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Cited by 189Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismExercise and Physiological Responses

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

Open access
de Oliveira dos Santos, Ana Rita, de Oliveira Zanuso, Bárbara, Miola, Vitor Fernando Bordin, Barbalho, Sandra Maria, Santos Bueno, Patrícia C., Flato, Uri Adrian Prync, Detregiachi, Claudia Rucco P., Buchaim, Daniela Vieira +5 more·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22052639PMC PMC7961600
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Abstract

Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

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Written from the paper’s full text.

TL;DR

This narrative review describes how adipokines, myokines, and hepatokines act through endocrine, paracrine, and autocrine crosstalk to influence insulin resistance, obesity, metabolic syndrome, and cardiovascular disease. It argues these organokines may serve as diagnostic/prognostic biomarkers and therapeutic targets, while calling for more in vivo and mechanistic studies.

Key findings

  • Adipose, skeletal muscle, and liver are the main endocrine organs producing adipokines, myokines, and hepatokines; these biomarkers can be harmful or beneficial and act together in a complex network affecting DM2, obesity, metabolic syndrome, and CVD.
  • Overweight individuals secrete more pro-inflammatory adipokines, leading to impaired immune response and greater susceptibility to inflammatory and infectious diseases; myostatin is elevated in pro-inflammatory environments alongside TNF-α, IL-1, resistin, and chemerin.
  • FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver; exercise shifts secretion toward anti-inflammatory organokines such as irisin, IL-6, IL-15, myonectin, adiponectin, and FGF21, which mitigate harmful effects of myostatin, TNF-α, resistin, chemerin, and fetuin-A.
  • The introduction cites an estimated 1.7 billion people vulnerable to health risks determined by body weight, 2.5 million deaths annually related to increased BMI expected to double by 2030, and CVDs responsible for approximately 17.9 million deaths per year, corresponding to 31% of total deaths worldwide.

Methods

  • Descriptive review using PUBMED-Medline, Embase, and Cochrane databases.
  • Mesh terms were adipokines, myokines, hepatokines, abdominal fat, insulin resistance, obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases.
  • Inclusion/exclusion was based on studies that included crosstalk among organokines, not just individual assessment of each one on insulin resistance, diabetes, obesity, metabolic syndrome, and cardiovascular complications.

Limitations

  • The paper states that in vivo experimental studies are further needed addressing crosstalk between adipokines, myokines, and hepatokines to support future clinical treatments, and that biochemical mechanisms of action of organokines are needed to guide future clinical trials.
  • Evident from the text: this is a descriptive/narrative review without a systematic protocol, risk-of-bias assessment, or quantitative synthesis; the search strategy and study selection are reported only briefly.

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Integrity signals

Registry

Crossref · 10.3390/ijms22052639

Cites

115 of 115 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

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  • Premisecitation

    Elevated leptin levels are associated with development, progression, and prognostication of non-alcoholic fatty liver disease.

    “Elevated levels of leptin were associated with development, progression and prognostication of non-alcoholic fatty liver disease (NAFLD) [41].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Polyzos, 2016, Circulating leptin in non-alcoholic fatty liver disease: A systematic review and meta-analysis, Diabetology source

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  • Premisecitation

    In adults with hyperleptinemia and leptin resistance, administration of metreleptin showed marginal benefits with a reduction in glycated hemoglobin.

    “In adults with hyperleptinemia and leptin resistance administration of metreleptin showed marginal benefits with a reduction in glycated hemoglobin [43].”
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  • Premisecitation

    Leptin is released by subcutaneous white adipose tissue.

    “Leptin is released by subcutaneous white adipose tissue (WAT) [39]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Premisecitation

    Organokines have specific associations with insulin resistance, diabetes mellitus, obesity, metabolic syndrome, and cardiovascular disease.

    “Therefore, they have specific associations with insulin resistance, diabetes mellitus, obesity, metabolic syndrome, and CVD [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Faramia, 2020, Metabolic adaptations after bariatric surgery: Adipokines, myokines and hepatokines, Curr. Opin. Pharmacol. source

      Not checked in the free run.

    • Rests on an assumption: Adipose, skeletal muscle, and hepatic tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines.
    • Rests on an assumption: These biomarkers can be harmful or beneficial and perform crosstalk through endocrine, paracrine, and autocrine pathways.
  • Premisecitation

    Hyperleptinemia contributes to the action of pro-inflammatory cytokines and continuous infiltration of M1 macrophages.

    “Hyperleptinemia contributes to the action of pro-inflammatory cytokines and continuous infiltration of M1 macrophages [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Oxidative stress and inflammation can impair insulin signaling and promote development of comorbidities such as type 2 diabetes mellitus, hypertension, and cardiovascular complications.

    “can impair insulin signaling and promote the development of comorbidities, such as type 2 diabetes mellitus (DM2), hypertension, and other factors that induce cardiovascular complications. [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Sofra, 2020, Adverse effects of sedentary lifestyles: Inflammation, and high-glucose induced oxidative stress—A double blind randomized clinical trial on diabetic and prediabetic patients, Health source

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    Premisecitation

    Adiponectin acts on insulin sensitivity, and its plasma reduction is related to insulin resistance and glucose intolerance, predisposing to advanced liver injury.

    “It acts on insulin sensitivity, and its plasma reduction is related to insulin resistance and glucose intolerance, predisposing to advanced liver injury [44].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Buechler, C., Haberl, E.M., Rein-Fischboeck, L., and Aslanidis, C. (2017). Adipokines in liver cirrhosis. Int. J. Mol. Sci., 18. source

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  • May combine two claims.

    Premisenone given

    Adiponectin is an antisteatotic, anti-inflammatory, and antifibrotic adipokine expressed by adipocytes from white and brown adipose tissue.

    “Adiponectin, an antisteatotic, anti-inflammatory, and antifibrotic adipokine, is expressed by adipocytes from WAT and brown adipose tissue (BAT).”
    Quote in the paperNot a substantial claim

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    Premisenone given

    Leptin increases oxidation and absorption of glucose and free fatty acid in skeletal muscles and promotes intrahepatic lipid reduction through fatty acid oxidation.

    “In addition, leptin increases the oxidation and absorption of glucose and free fatty acid (FFA) in skeletal muscles and promotes intrahepatic lipid reduction through fatty acid oxidation (Figure 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Eating behavior, delimited by cultural and social aspects, has a substantial impact on health conditions and the development of cardiovascular diseases and inflammatory complications.

    “Eating behavior, delimited by cultural and social aspects, has a substantial impact on health conditions and the development of cardiovascular diseases and inflammatory complications [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Huber, B.C., Steffen, J., Schlichtiger, J., and Brunner, S. (2020). Altered nutrition behavior during COVID-19 pandemic lockdown in young adults. Eur. J. Nutr. source

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    Premisecitation

    In obesity, adipose tissue hypertrophy is directly related to chronic low-grade inflammation and an increase in chemotactic molecules, reduction in adiponectin levels, and onset of leptin resistance.

    “In obesity, its hypertrophy is directly related to chronic low-grade inflammation and an increase in chemotactic molecules, in addition to a reduction in adiponectin levels and the onset of leptin resistance.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Faramia, 2020, Metabolic adaptations after bariatric surgery: Adipokines, myokines and hepatokines, Curr. Opin. Pharmacol. source

      Not checked in the free run.

    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

    • cites [13] Song, P., Kwon, Y., Joo, J.Y., Kim, D.G., and Yoon, J.H. (2019). Secretomics to discover regulators in diseases. Int. J. Mol. Sci., 20. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Metreleptin is a recombinant methyl-human leptin hormone showing efficacy in children with congenital leptin deficiency for reversal of obesity and metabolic improvement.

    “Metreleptin is a recombinant methyl-human leptin hormone showing efficacy in children with congenital leptin deficiency reversal of obesity and metabolic improvement [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Farooqi, 1999, Effects of recombinant leptin therapy in a child with congenital leptin deficiency, N. Engl. J. Med. source

      Not checked in the free run.

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    Premisecitation

    In obesity, increase in leptin levels is associated with leptin resistance and increase in reactive oxygen species, IL-6, TNF-alpha, and chemokines.

    “In obesity, the increase in leptin levels is associated with the state of leptin resistance, in addition to the increase in reactive oxygen species (ROS), IL-6, TNF-α, and chemokines.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Leptin stimulates division of hepatic stellate cells and synthesis of pro-fibrogenic and pro-inflammatory factors in these cells, and induces synthesis of TGF-beta in Kupffer cells.

    “Leptin stimulates the division of hepatic stellate cells and the synthesis of pro-fibrogenic and pro-inflammatory factors in these cells; moreover, it induces the synthesis of transforming growth factor b (TGFβ) in Kupffer cells [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Merli, 2019, Sarcopenic obesity in fatty liver, Curr. Opin. Clin. Nutr. Metab. Care source

      Not checked in the free run.

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    Premisenone given

    Leptin acts as an endocrine signal by reducing appetite and stimulating energy expenditure by activating POMC-expressing neurons and inhibiting hypothalamic AgRP and NPY.

    “acts as an endocrine signal by reducing appetite and stimulating energy expenditure by activating pro-opiomelanocortin (POMC)—expressing neurons, inhibiting the hypothalamus agouti-related protein (AgRP) and neuropeptide Y (NPY).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Leptin and adiponectin are classic adipokines of adipose tissue and have a substantial relationship in the pathogenesis of obesity and metabolic complications.

    “Leptin and adiponectin (Table 1) are the classic adipokines of adipose tissue and have a substantial relationship in the pathogenesis of obesity and metabolic complications [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Lund, 2020, Leptin, adiponectin, and their ratio as markers of insulin resistance and cardiometabolic risk in childhood obesity, Pediatr. Diab. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The main circulating form of omentin is omentin-1, known as interleukin-1, expressed in visceral adipose tissue, and its levels are regulated by FGF-21, dexamethasone, glucose, and insulin.

    “The main circulating form of omentin is omentin-1, known as interleukin-1, expressed in visceral tissue adipose, and its levels are regulated by fibroblast growth factor-21, dexamethasone, glucose, and insulin [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Watanabe, 2017, Adipose tissue-derived omentin-1 function and regulation, Compr. Physiol. source

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    Premisecitation

    IL-6 is produced by macrophages and stimulated by activation of NF-kappaB and acts in inhibiting expression of IRS1 and GLUT4 in adipocytes.

    “It is produced by macrophages and stimulated by the activation of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and acts in inhibiting the expression of insulin receptor substrate 1 (IRS1) and glucose transporter type 4 (GLUT4) in adipocytes [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

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    Premisecitation

    Asprosin is an orexigenic hormone induced by fasting and produced by white adipose tissue; it increases food consumption and body weight through AgRP neurons and accelerates liver glucose production by activating the G protein-cAMP-PKA pathway.

    “It is an orexigenic hormone induced by fasting and produced by WAT, and increases food consumption and body weight through Agouti-related protein neurons (AgRP), and accelerates the production of liver glucose, activating the G protein-cAMP-protein kinase A (PKA) pathway [16,17].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Duerrschmid, 2017, Asprosin is a centrally acting orexigenic hormone, Nat. Med. source

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    • cites [17] Romere, 2016, Asprosin, a fasting-induced glucogenic protein hormone, Cell source

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    Premisecitation

    Asprosin is associated with modulation of cardiac mitochondrial functions, and in patients with dilated cardiomyopathy, elevated asprosin level is associated with fewer adverse cardiovascular issues in five years.

    “Another interesting study showed that asprosin is associated with the modulation of cardiac mitochondrial functions and in patients with dilated cardiomyopathy patients, elevated asprosin level is associated with less adverse cardiovascular issues in five years.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Wen, M.S., Wang, C.Y., Yeh, J.K., Chen, C.C., Tsai, M.L., Ho, M.Y., Hung, K.C., and Hsieh, I.C. (2020). The role of Asprosin in patients with dilated cardiomyopathy. BMC Cardiovasc. Dis., 20. source

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    Premisecitation

    FGF21 increases expression of UCP1 and other thermogenic genes and stimulates expression of adiponectin in the bloodstream and white adipose tissue.

    “In addition, it increases the expression of uncoupling protein 1 (UCP1) and other thermogenic genes and stimulates the expression of adiponectin in the bloodstream and WAT [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Mehta, 2019, Fibroblast growth factor 21 and browning of white adipose tissue, Front. Physiol. source

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    Premisecitation

    SFRP5 is associated with comorbidities such as obesity, type 2 diabetes mellitus, insulin resistance, and atherosclerosis, inhibiting Wnt5a and non-canonical Wnt family and regulating expression of pro-inflammatory cytokines.

    “SFRP5 is associated with comorbidities such as obesity, DM2, insulin resistance, and atherosclerosis, inhibiting the wingless-type family member 5a signaling (Wnt5a) and the non-canonical Wnt family and regulating the expression of pro-inflammatory cytokines [14,21].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

    • cites [21] Wang, 2020, Sfrp5/Wnt5a and leptin/adiponectin levels in the serum and the periarterial adipose tissue of patients with peripheral arterial occlusive disease, Clin. Biochem. source

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  • May combine two claims.

    Premisenone given

    Adiponectin contributes significantly to anti-inflammatory action, thermogenesis, lipolysis, and oxidation of fatty acids in skeletal muscle and liver.

    “This adipokine contributes significantly to anti-inflammatory action, thermogenesis, lipolysis, and oxidation of fatty acids in skeletal muscle and liver.”
    Quote in the paperNot a substantial claim

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    Premisenone given

    SPARC is expressed in most tissues and is one of the proteins in the extracellular matrix of adipose tissue.

    “Although initially found in bone tissue, SPARC is expressed in most tissues, being one of the proteins in the extracellular matrix of adipose tissue.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Vaspin improves glucose intolerance and insulin sensitivity and reduces synthesis of pro-inflammatory cytokines.

    “However, the function of vaspin is to improve glucose intolerance and insulin sensitivity and reduce the synthesis of pro-inflammatory cytokines [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Kukla, 2020, Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma, Clin. Exp. Hepatol. source

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    Premisenone given

    CTRP action occurs through several receptors, including adipoR1 and adipoR2.

    “Its action occurs through several receptors, including adipoR1 and adipoR2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Asprosin is encoded by the FBN1 locus and has a role in mediation of the lipodystrophy phenotype.

    “Asprosin, which is encoded by the FBN1 locus, has a role in the mediation of the lipodystrophy phenotype [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Lin, 2020, Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1, Mol. Genet. Genom. Med. source

      Not checked in the free run.

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    Premisecitation

    Plasma levels of adiponectin can be reduced with increase in pro-inflammatory cytokines TNF-alpha and IL-6 present in obesity, in addition to levels of myostatin, a myokine that can elevate adipose tissue mass.

    “Plasma levels of adiponectin can be reduced with the increase in pro-inflammatory cytokines such as TNF-α and IL-6, present in obesity, in addition to the levels of myostatin, a myokine that can elevate the adipose tissue mass [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Mikolasevic, 2020, Nonalcoholic fatty liver disease and sarcopenia: Where do we stand?, Can. J. Gastroenterol. Hepatol. source

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    Premisecitation

    Obese people have a high concentration of asprosin, and it is closely related to insulin resistance in humans, with higher serum asprosin levels identified in patients with type 2 diabetes mellitus.

    “In a clinical study, it was found that obese people have a high concentration of asprosin, and it is also closely related to insulin resistance in humans, which is proven when higher serum levels of asprosin are identified in patients with DM2 [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Kim, 2020, Newly discovered adipokines: Pathophysiological link between obesity and cardiometabolic disorders, Front. Physiol. source

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    Premisecitation

    FSTL1 is an adipokine and myokine reported as a pre-adipocyte/adipocyte-secreted protein, has pro-inflammatory action, and has a possible relationship with overweight and obesity.

    “Follistatin-like 1 (FSTL1), an adipokine and myokine reported as a pre-adipocyte/adipocyte-secreted protein, has a pro-inflammatory action and possible relationship with overweight and obesity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Omentin acts to improve insulin sensitivity and glucose absorption and acts as an anti-atherosclerotic factor.

    “In turn, omentin acts to improve insulin sensitivity and glucose absorption and acts as an anti-atherosclerotic factor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Chemerin is secreted as an inactive molecule, is activated by inflammatory and coagulation serine proteases, accentuates glucose intolerance, and makes insulin signaling difficult.

    “On the other hand, the adipokine named chemerin, which is secreted and an inactive molecule, is activated by inflammatory and coagulation serine proteases, accentuates glucose intolerance, and makes insulin signaling difficult.”
    Quote in the paperNot a substantial claim

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    Premisenone given

    FAM19A5 is released by adipose tissue, and its expression is reduced in obesity.

    “On the other hand, the family with sequence similarity to 19 member A5 (FAM19A5), initially demonstrated in mice, is released by adipose tissue, and its expression is reduced in obesity.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Adiponectin action begins with binding to AdipoR1 or 2 receptors and activation of AMPK, leading to reduced lipogenesis and gluconeogenesis and increased glucose absorption by skeletal muscle and white adipose tissue.

    “Its action begins with the binding to its AdipoR1 or 2 receptors and the activation of AMP-activated protein kinase (AMPK), leading to reduced lipogenesis and gluconeogenesis and increased glucose absorption by skeletal muscle and WAT [46].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Fang, 2018, Adiponectin regulation and function, Comprehensive Physiology source

      Not checked in the free run.

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    Premisecitation

    In humans, FGF21 is responsible for browning of white adipose tissue, activation of brown adipocytes, and lipolysis.

    “In humans, FGF21 is responsible for the browning of WAT, activation of brown adipocytes, and lipolysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Vaspin is a protein that inhibits serine protease, is found in greater quantities in obese individuals with type 2 diabetes mellitus, and is expressed by adipose tissue and skeletal muscle.

    “In the same perspective, visceral adipose tissue-derived serpin (vaspin), a protein that inhibits serine protease, is also found in greater quantities in obese individuals with DM2 and expressed by adipose tissue and skeletal muscle [53].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Nicholson, T., Church, C., Tsintzas, K., Jones, R., Breen, L., Davis, E.T., Baker, D.J., and Jones, S.W. (2019). Vaspin promotes insulin sensitivity of elderly muscle and is upregulated in obesity. J. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chemerin acts through ChemR23, and its receptors are mostly concentrated in adipose tissue and hepatocytes, despite existing throughout the human body.

    “Its action occurs through the chemerin receptor (ChemR) 23, and its receptors are mostly concentrated in adipose tissue and hepatocytes, despite existing throughout the human body [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Shi, 2019, Cytokines and abnormal glucose and lipid metabolism, Front. Endocrinol. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CTRPs are a family of adipokines with a structure similar to adiponectin, involved in regulation of glucose and fat metabolism in peripheral tissues, food intake, and inflammatory processes of adipose tissue.

    “C1q/TNF-related proteins (CTRPs) are related to a family of adipokines with a structure similar to adiponectin, involved in the regulation of glucose and fat metabolism in peripheral tissues, food intake, and inflammatory processes of adipose tissue [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Lei, 2017, C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance, J. Biol. Chem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Resistin is a mediator of obesity-related insulin resistance, a pro-inflammatory adipokine correlated with fat mass that acts on endothelial dysfunction and cardiovascular diseases.

    “Resistin, a mediator of obesity-related insulin resistance, is a pro-inflammatory adipokine correlated with fat mass that acts on endothelial dysfunction and cardiovascular diseases [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Musovic, 2020, Resistin is co-secreted with adiponectin in white mouse adipocytes, Biochem. Biophys. Res. Commun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 in adipose tissue has pro-inflammatory characteristics, is directly related to BMI, and is augmented in individuals with insulin resistance, obesity, and type 2 diabetes mellitus.

    “In the same perspective, IL-6, in adipose tissue, has pro-inflammatory characteristics, being directly related to the BMI, and is augmented in individuals with insulin resistance, obesity, and DM2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In mice, CTRP6 expression, regulated for adipose tissue in obesity and diabetes, is secreted by stromal vascular cells and macrophages, and its increased expression substantially compromised glucose disposal in peripheral tissues.

    “Studies in mice have demonstrated that the expression of CTRP6, regulated for adipose tissue in obesity and diabetes, is secreted by stromal vascular cells and macrophages, and its increased expression substantially compromised the disposal of glucose in peripheral tissues [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Recinella, 2020, Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases, Front. Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Fetuin-A is classically considered a hepatokine, is a natural insulin inhibitor tyrosine kinase, and is associated with insulin resistance and inflammation in rodents and humans.

    “Fetuin-A (Fet-A), classically considered a hepatokine, is a natural insulin inhibitor tyrosine kinase and is associated with insulin resistance and inflammation in rodents and humans.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    WISP1 is an adipokine associated with extracellular matrix, expressed for visceral and subcutaneous adipose tissue, and stimulates cytokine response in macrophages associated with adipose tissue.

    “From the same perspective, the wingless-type inducible signaling pathway protein-1 (WISP1), an adipokine associated with the extracellular matrix, is expressed for visceral and subcutaneous tissue adipose and stimulates the cytokine response in macrophages associated with tissue adipose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Apelin is released mainly in resistance exercises and has an anti-inflammatory role and essential actions in metabolism, control of cardiac muscles and blood pressure, new vessel formation, and control of cell cycle and death.

    “Apelin, released mainly in resistance exercises, has an important anti-inflammatory role and other essential actions in metabolism, control of cardiac muscles and blood pressure, new vessels’ formation, and control of cell cycle and death.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Progranulin is secreted by adipocytes from visceral adipose tissue, macrophages, chondrocytes, and other cells, and has anti-inflammatory properties due to competition with TNFR1 and TNFR2.

    “On the other hand, the glycoprotein progranulin, secreted by adipocytes from visceral tissue adipose, macrophages, chondrocytes, and other cells, has anti-inflammatory properties due to competition with TNF-α receptors (TNFR1 and TNFR2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Each myokine appears to be related to a specific type of muscle fiber and different physical exercise modalities.

    “Each myokine appears to be related to a specific type of muscle fiber and different physical exercise modalities [56] (Table 2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

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  • May combine two claims.

    Interpretationreasoning

    Induction of adipocyte browning by irisin suppresses adipogenesis and cholesterol synthesis and optimizes lipid oxidation and lipidic homeostasis.

    “Therefore, induction of adipocyte browning by irisin suppresses adipogenesis and cholesterol synthesis and optimizes lipid oxidation and lipidic homeostasis by extension.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Myokines are expressed mainly in physical activities or absence, allowing communication with other body tissues, showing actions that can be beneficial for most myokines or related to metabolic dysfunctions.

    “These molecules are expressed mainly in physical activities or absence, allowing its communication with other body tissues, thereby showing actions that can be considered beneficial for most myokines or related to metabolic dysfunctions [8,14].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Barbalho, S.M., Flato, U.A.P., Tofano, R.J., Goulart, R.A., Guiguer, E.L., Detregiachi, C.R.P., Buchaim, D.V., Araújo, A.C., Buchaim, R.L., and Reina, F.T.R. (2020). Physical exercise and myokines: Relationships with sarcopenia and cardiovascular complications. Int. J. Mol. Sci., 21. source

      Not checked in the free run.

    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a clinical study by Mikolajczak et al., FGF21 levels are increased in obesity, possibly as an adaptive mechanism against insulin resistance and its consequences.

    “Despite this, the clinical study by Mikolajczak et al. showed that FGF21 levels are increased in the state of obesity, possibly as an adaptive mechanism against insulin resistance and its consequences [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Mikolajczak, 2017, Serum FGF21 in girls with anorexia nervosa—Comparison to normal weight and obese female adolescents, Neuro Endocrinol. Lett.

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Despite its pro-inflammatory label, IL-6 levels increase after physical exercise, which promotes secretion of IL-10, an IL-1 antagonist and possible inhibitor of TNF-alpha, characterizing an anti-inflammatory environment after increased IL-6 released by muscle tissue.

    “Despite the pro-inflammatory cytokine label, mainly due to their role as an adipokine, IL-6 levels are increased after physical exercises, which promotes the secretion of interleukin-10 (IL-10), an IL-1 antagonist and possible inhibitor of TNF-α, characterizing an anti-inflammatory environment after increasing the concentration of IL-6 released by muscle tissue.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Follistatin is a myokine and hepatokine, released in the context of physical activity, which opposes myostatin's actions by directly inhibiting it through binding.

    “In contrast, there is follistatin, a myokine, and hepatokine, released in the context of physical activity, which is opposed to myostatin’s actions, directly inhibiting it through binding.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ZAG regulates lipogenesis and lipolysis enzymes, stimulates adiponectin production, and promotes browning of white adipose tissue.

    “Its action is in regulating lipogenesis and lipolysis enzymes, in the stimulation of adiponectin production, and the browning of WAT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Visfatin is an adipokine secreted by adipose tissue, a class type II phosphoribosyltransferase homodimer, and increases in obese people.

    “Another adipokine secreted by adipose tissue is visfatin, a class type II phosphoribosyltransferase homodimer, which increases in obese people.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Visfatin secretion is more significant in subcutaneous adipose tissue and is associated with enzymatic activity such as NAMPT.

    “Its secretion is more significant in the subcutaneous adipose tissue and is associated with an enzymatic activity such as nicotinamide phosphoribosyltransferase (NAMPT) [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Franco-Trepat, E., Guillán-Fresco, M., Alonso-Pérez, A., Jorge-Mora, A., Francisco, V., Gualillo, O., and Gómez, R. (2019). Visfatin connection: Present and future in osteoarthritis and osteoporosis. J. Clin. Med., 8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies point to a relationship between high levels of irisin and low atherosclerosis burden in coronary arteries, proving its cardioprotective effects.

    “Studies point to a relationship between high levels of irisin and low atherosclerosis burden in coronary arteries, proving its cardioprotective effects [8].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Barbalho, S.M., Flato, U.A.P., Tofano, R.J., Goulart, R.A., Guiguer, E.L., Detregiachi, C.R.P., Buchaim, D.V., Araújo, A.C., Buchaim, R.L., and Reina, F.T.R. (2020). Physical exercise and myokines: Relationships with sarcopenia and cardiovascular complications. Int. J. Mol. Sci., 21. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Follistatin contributes to increase in muscle mass, optimizing glucose uptake by skeletal muscle and white adipose tissue lipolysis.

    “Thus, follistatin contributes to the increase in muscle mass, optimizing glucose uptake by SkM and WAT lipolysis [11,13].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

    • cites [13] Song, P., Kwon, Y., Joo, J.Y., Kim, D.G., and Yoon, J.H. (2019). Secretomics to discover regulators in diseases. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Myostatin inhibition may be a therapeutic target for muscle mass loss disorders such as atrophy, sarcopenia, and cancer.

    “Possibly, myostatin inhibition may be a therapeutic target for muscle mass loss disorders, such as atrophy, sarcopenia, and cancer [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Mikolasevic, 2020, Nonalcoholic fatty liver disease and sarcopenia: Where do we stand?, Can. J. Gastroenterol. Hepatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FGF21 increases insulin sensitivity, reduces plasma glucose levels, and has lipolytic activity that decreases plasma triglyceride levels.

    “It increases insulin sensitivity, reduces plasma glucose levels, and has lipolytic activity, which decreases plasma triglyceride levels [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Faramia, 2020, Metabolic adaptations after bariatric surgery: Adipokines, myokines and hepatokines, Curr. Opin. Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A drop in myonectin levels, which can be caused by physical inactivity or a high-fat diet, is related to excess circulating free fatty acids and subsequent accumulation in other tissues and insulin resistance.

    “A drop in myonectin levels, which can be caused by physical inactivity or a high-fat diet, is related to excess circulating FFA and subsequent accumulation in other tissues and insulin resistance [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Mehta, 2019, Fibroblast growth factor 21 and browning of white adipose tissue, Front. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-15 helps in reduction of visceral adipose tissue without reducing subcutaneous fat, showing performance in muscle-fat crosstalk.

    “Additionally, it helps in the reduction in visceral adipose tissue without reducing subcutaneous fat, showing performance in muscle-fat crosstalk [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Nesfatin-1 is involved in energy homeostasis and satiety induction and is described as an anorexigenic molecule secreted by subcutaneous adipose tissue, pancreatic cells, gastric mucosa, and hypothalamus.

    “Nesfatin-1, in turn, involved in energy homeostasis and satiety induction, is described as an anorexigenic molecule secreted by subcutaneous adipose tissue, pancreatic cells, gastric mucosa, and hypothalamus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Irisin is a transmembrane protein with a type III fibronectin domain secreted after physical exercise, which participates in browning of white adipose tissue by increasing UCP1 and respiratory chain of brown adipose tissue, promoting energy expenditure especially as heat, contributing to weight loss.

    “It is a transmembrane protein with a type III fibronectin domain secreted after physical exercise, which has shown participation in the browning of white tissue adipose (WAT) process by increasing the expression of uncoupling protein-1, the respiratory chain of BAT, which promotes energy expenditure especially in the form of heat, contributing to weight loss [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Myonectin is released in resistance modalities and acts on lipid metabolism, increasing lipid uptake by adipose tissue and liver and decreasing plasma free fatty acid concentration.

    “Furthermore, released in resistance modalities, myonectin acts on the metabolism of lipids, increasing their uptake by adipose tissue and liver, thus decreasing the plasma concentration of FFA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    IL-6 is the first myokine described, often characterized as a pro-inflammatory cytokine produced by various tissues, and is considered a myokine, adipokine, and hepatokine.

    “Interleukin-6 (IL-6), the first myokine to be described, is often characterized as a pro-inflammatory cytokine produced by various tissues, being considered myokines, adipokines, and hepatokine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Visfatin in high concentrations causes insulin resistance and pancreatic beta-cell dysfunction and produces inflammation in adipocytes.

    “Visfatin in high concentrations causes insulin resistance and pancreatic beta-cell dysfunction and produces inflammation in adipocytes [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Kumari, 2018, Adipokine visfatin’s role in pathogenesis of diabesity and related metabolic derangements, Curr. Mol. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some experimental studies point to a possible correlation between increased levels of IL-6 and inhibition of appetite.

    “Moreover, some experimental studies point to a possible correlation between increased levels of IL-6 and inhibition of appetite [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Yuan, 2020, Asprosin: A novel player in metabolic diseases, Front. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Irisin appears to increase insulin sensitivity, promoting glucose transporter mobilization in insulin-dependent tissues, and improves metabolic syndrome and cardiovascular disease.

    “In addition, irisin appears to increase insulin sensitivity, promoting glucose transporter mobilization in insulin-dependent tissues, and improves metabolic syndrome and CVD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    IL-15 has anti-inflammatory properties, mainly by inhibiting expression of TNF-alpha, which plays a role in oxidative stress.

    “IL-15 has anti-inflammatory properties, mainly by inhibiting the expression of TNF-α, which plays a role in oxidative stress.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    IL-15 prevents reduction in muscle mass and increases uptake of glucose by skeletal muscle by stimulating mobilization of GLUT4, contributing to muscle hypertrophy.

    “It also prevents the reduction in muscle mass and increases the uptake of glucose by skeletal muscle by stimulating the mobilization of glucose transporters 4 (GLUT 4), contributing to muscle hypertrophy [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Shi, 2019, Cytokines and abnormal glucose and lipid metabolism, Front. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    FGF21 is produced by several tissues and is classified as a myokine, adipokine, and hepatokine.

    “Fibroblast growth factor 21 (FGF21) is produced by several tissues classified as myokine, adipokines, and hepatokine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In rodents, injections of nesfatin-1 inhibit food intake, and its lack in the brain causes an increase in appetite, fat, and body weight.

    “In rodents, injections of nesfatin-1 inhibit food intake, and its lack in the brain causes an increase in appetite, fat, and body weight.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Reduction in muscle mass mediated by myostatin facilitates appearance of metabolic disorders such as insulin resistance and accumulation of fat in liver, since skeletal muscle is the main source of glucose-dependent glucose uptake.

    “This reduction in muscle mass, mediated by myostatin, facilitates the appearance of metabolic disorders, such as resistance to insulin and accumulation of fat in the liver, since skeletal muscle is the main source of glucose-dependent glucose uptake.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ZAG is expressed by both white and brown adipose tissue and directly accelerates lipid metabolism.

    “On the other hand, the adipokine zinc-α2-glycoprotein (ZAG) is expressed by both white and BAT and directly accelerates lipid metabolism [38].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Zhang, 2020, Zinc-α2-glycoprotein knockout influenced genes expression profile in adipose tissue and decreased the lipid mobilizing after dexamethasone treatment in mice, Horm. Metab. Res. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Myonectin shows positive effects on the cardiovascular system, which may reveal a potential therapeutic target in cardiovascular disease treatment.

    “This myokine shows positive effects on the cardiovascular system, which may reveal a potential therapeutic target in CVD treatment [8].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Barbalho, S.M., Flato, U.A.P., Tofano, R.J., Goulart, R.A., Guiguer, E.L., Detregiachi, C.R.P., Buchaim, D.V., Araújo, A.C., Buchaim, R.L., and Reina, F.T.R. (2020). Physical exercise and myokines: Relationships with sarcopenia and cardiovascular complications. Int. J. Mol. Sci., 21. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nesfatin-1 can regulate gastric distension and motility via the melanocortin pathway in the central nucleus of the amygdala.

    “In addition, nesfatin-1 can regulate gastric distension and motility via the melanocortin pathway in the central nucleus of the amygdala [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Recinella, 2020, Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases, Front. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hyperprogranulinemia present in obesity is associated with insulin resistance and deficient insulin signaling, whereas progranulin deficiency can protect from diet-induced insulin resistance.

    “However, hyperprogranulinemia present in obesity is associated with insulin resistance and deficient insulin signaling, whereas its deficiency can protect from diet-induced insulin resistance [31,32].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [31] Abella, 2017, Leptin in the interplay of inflammation, metabolism and immune system disorders, Nat Rev. Rheumatol. source

      Not checked in the free run.

    • cites [32] Korolczuk, 2017, Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension, Curr. Pharm. Design source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, overexpression of adropin improves insulin sensitivity and glucose tolerance.

    “On the other hand, it has been seen that in mice, the overexpression of adropin reduces weight gain, attenuates hepatosteatosis, increases fatty acid oxidation throughout the body, improves insulin sensitivity, and improves glucose tolerance [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hepatokines are proteins produced by the liver that can worsen or improve metabolic conditions.

    “Hepatokines are proteins produced by the liver that have recently been discovered as new hormones, which can worsen or improve metabolic conditions [64].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Choi, 2016, The impact of organokines on insulin resistance, inflammation, and atherosclerosis, Endocrinol. Metab. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Decorin is involved in skeletal muscle hypertrophy.

    “It is secreted by skeletal muscle cells and is involved in the skeletal muscle hypertrophy and regulates muscle growth with the practice of physical exercise [63].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., and Guzik, P. (2021). Effect of various exercise regimens on selected Exercise-induced cytokines in healthy people. Int. J. Environ. Res. Public Health, 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In mice, plasma levels of adropin increase with feeding and decrease with fasting.

    “Studies have shown that in mice, plasma levels of adropin increase with feeding and decrease with fasting.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fetuin-A concentration interferes with the insulin signaling cascade and the translocation of GLUT4 in insulin target tissues.

    “This metabolic pattern is caused due to the concentration of fetuin-A interfering with the insulin signaling cascade and the translocation of GLUT4 in insulin target tissues [79].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Iroz, 2015, Hepatokines: Unlocking the multi-organ network in metabolic diseases, Diabetologia source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some studies address the role of SPARC in activating caspase-3 and caspase-8 dependent apoptosis, which reveals a potential benefit of physical exercise in decreasing incidence of colon cancer.

    “Some studies address the role of SPARC in activating caspase-3 and caspase-8 dependent apoptosis, which reveals a potential benefit of physical exercise in decreasing the incidence of colon cancer [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Aoi, 2019, Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation, FASEB J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BDNF is released by muscle and brain tissue after exercise; unlike other myokines, it is not released into the bloodstream.

    “The brain-derived neurotrophic factor (BDNF) is also released by muscle and brain tissue after exercise; however, unlike other myokines, it is not released into the bloodstream [61].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Cooper, 2018, On the run for hippocampal plasticity, Cold Spring Harbor Perspect. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SPARC is released in episodes of resistance exercises and muscle hypertrophy and is related to optimization of glucose uptake by increased expression and translocation of GLUT4 by activating AMPK signaling pathway.

    “SPARC is released in episodes of resistance exercises and muscle hypertrophy and has also been related to the optimization of glucose uptake by increased expression and translocation of GLUT 4 by activating the AMPK signaling pathway [56].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BDNF is related to glucose and lipid metabolism regulation and increased insulin sensitivity when released by muscle.

    “Besides that, it is also related to glucose and lipid metabolism regulation and increased insulin sensitivity when released by muscle [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exercise stimulates release of myokines such as cathepsin B and irisin, which cross the blood-brain barrier to induce cerebral BDNF secretion.

    “The study performed by Pedersen [56] suggests that exercise stimulates the release of myokines, such as cathepsin B and irisin, which in turn cross the blood–brain barrier to induce cerebral BDNF secretion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    BDNF acts primarily on neurons through tyrosine receptor kinases, allowing their growth and survival and playing a fundamental role for memory and learning.

    “This acts primarily on neurons through tyrosine receptor kinases (Trk), allowing their growth and survival and playing a fundamental role for memory and learning.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In vitro, endothelial cells treated with adropin had greater proliferation, migration, formation of a capillary-like tube, and positive regulation of eNOS expression.

    “Still, in this respect, there is increasing evidence that adropin is a biomarker of cardiovascular dysfunction, initially because in vitro tests showed that endothelial cells treated with adropin had greater proliferation, migration, formation of a capillary-like tube, and positive regulation of the expression of nitric oxide endothelial synthase (eNOS).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Zhao, 2015, Serum adropin level in patients with stable coronary artery disease, Heart Lung Circulat. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, overexpression of adropin reduces weight gain and attenuates hepatosteatosis.

    “On the other hand, it has been seen that in mice, the overexpression of adropin reduces weight gain, attenuates hepatosteatosis, increases fatty acid oxidation throughout the body, improves insulin sensitivity, and improves glucose tolerance [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SPARC is able to inhibit formation of adipose tissue, increase release of insulin, and promote erythropoiesis.

    “It is also able to inhibit the formation of adipose tissue, increase the release of insulin and promote erythropoiesis [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ANGPTL4 acts on WAT, stimulating lipolysis and decreasing lipoprotein lipase (LPL) action.

    “This hepatokine also acts on WAT, stimulating lipolysis and decreasing the enzyme lipoprotein lipase (LPL) action, that is, reducing the hydrolysis of triglycerides in circulating lipoproteins to FFA and reducing the accumulation of lipids in the white tissue adipose [75].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Ennequin, 2019, Role of exercise-induced hepatokines in metabolic disorders, Am. J. Physiol. Endocrinol. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High serum levels of seleno-protein are associated with metabolic diseases, insulin resistance, and increased reactive oxygen species (ROS) via activation of AMPK.

    “When seleno-protein is found in high serum levels, it is associated with metabolic diseases, insulin resistance, and increased ROS via the activation of AMPK, and it influences the drop in concentrations of irisin, meteorin-like (METRNL), and β-aminoisobutyric acid (BAIBA), which consequently attenuates the loss of fat mass induced by physical exercises [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, follistatin overexpression is associated with insulin resistance in WAT, elevated hepatic glucose production, and glucose intolerance.

    “In addition, studies with mice have shown that follistatin overexpression is associated with insulin resistance in WAT, elevated hepatic glucose production, and glucose intolerance [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased seleno-protein P increases insulin resistance, accumulates fat in adipose tissue, and aggravates risks of developing atherosclerosis.

    “In addition, studies have shown that intermittent hypoxia generates stress that increases the levels of seleno-protein P in human hepatocytes, increasing insulin resistance, accumulating fat in adipose tissue, and aggravating risks of developing atherosclerosis [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Chemerin is produced by the liver and contributes to a decrease in glucose homeostasis.

    “Chemerin is not only an adipokine, but is also produced by the liver and contributes to the decrease in glucose homeostasis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Follistatin originates from the liver and rises when the glucagon-to-insulin ratio increases in the case of fasting and aerobic and resistance exercise.

    “Follistatin originates from the liver and rises when the glucagon-to-insulin ratio increases in the case of fasting and aerobic and resistance exercise [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Perakakis, 2018, Physiology of activins/follistatins: Associations with metabolic and anthropometric variables and response to exercise, J. Clin. Endocrinol. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elevated LECT2 is associated with metabolic stress, which impairs insulin signal transduction.

    “Thus, it has been shown that elevated LECT2 is associated with metabolic stress, which impairs insulin signal transduction, has a responsibility to promote and express adhesion molecules, and increases the appearance of pro-inflammatory cytokines.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In humans, activin E reduces lipolysis and increases fat accumulation in adipocytes.

    “However, in humans, activin E has been reported to reduce lipolysis and increase fat accumulation in adipocytes.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Sugiyama, M., Kikuchi, A., Misu, H., Igawa, H., Ashihara, M., Kushima, Y., Honda, K., Suzuki, Y., Kawabe, Y., and Kaneko, S. (2018). Inhibin βE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples. PLoS ONE, 13. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Overexpression of ANGPTL6 results in insulin sensitivity and elevated energy expenditure.

    “On the other hand, overexpression of this organokine results in insulin sensitivity and elevated energy expenditure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Plasma levels of TNF-α in exercise are reduced, although its expression in adipose tissue is not affected.

    “Despite this, IL-6 released during physical exercise can improve glucose and lipid metabolism, while plasma levels of TNF-α in exercise are reduced, although its expression in adipose tissue is not affected [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity.

    “In parallel, myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity, which promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adipokines can modulate bone mineral density and bone turnover as well as skeletal muscle catabolism in aging.

    “In addition to being involved in disease metabolism, adipokines can modulate bone mineral density and bone turnover as well as skeletal muscle catabolism in aging [97].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Makowski, 2020, Chapter four—Myokines: The endocrine coupling of skeletal muscle and bone, Advances in Clinical Chemistry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    ANGPTL6 is highly expressed in obesity, augments lipid accumulation in skeletal muscle and liver, reduces energy expenditure, and increases insulin resistance.

    “ANGPTL6 is highly expressed in obesity, augmented lipid accumulation in skeletal muscle and liver, reduced energy expenditure, and increased insulin resistance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Insulin suppression leads to an increase in plasma fatty acid and consequent absorption by liver and muscle tissue, creating intracellular lipotoxic environments that prevent the translocation of GLUT4 in skeletal muscles and adipose tissue.

    “Insulin suppression leads to an increase in plasma fatty acid and consequent absorption by liver and muscle tissue, creating intracellular lipotoxic environments that prevent the translocation of GLUT4 in skeletal muscles and adipose tissue [104,105].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [104] Nayak, 2020, Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue, Physiol. Rep.

      Not checked in the free run.

    • cites [105] Goedeke, 2019, Emerging pharmacological targets for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes, Ann. Rev. Pharmacol. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many studies point to a decrease in myostatin through physical exercise, with positive effects in combating insulin resistance and reducing fat accumulation and muscle hypertrophy.

    “Many studies point to a decrease in myostatin through physical exercise, with positive effects in combating insulin resistance and reducing fat accumulation and muscle hypertrophy [95].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Leal, 2018, Physical exercise-induced myokines and muscle-adipose tissue crosstalk: A review of current knowledge and the implications for health and metabolic diseases, Front. Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    ANGPTL3 is expressed and released by the liver and works as a regulator of plasma triglyceride levels.

    “ANGPTL3 is expressed and release by the liver and works as a regulator of plasma triglyceride levels, positively associated with glycemia, and insulin levels in patients with insulin resistance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Together, these cytokines induced in a healthy environment optimize the secretion and action of insulin, favor energy expenditure, reduce the storage of visceral fat, and stimulate polarization of MφM2 and reduction in Toll-like receptors (TLRs), decreasing the inflammatory pattern.

    “Together, these cytokines induced in a healthy environment optimize the secretion and action of insulin; favor energy expenditure; reduce the storage of visceral fat; and, consequently, stimulate polarization of MϕM2 and reduction in Toll-like receptors (TLRs), decreasing the inflammatory pattern [11,102].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

    • cites [102] Gannar, 2018, Myokines, physical activity, insulin resistance and autoimmune diseases, Immunol. Lett. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Myostatin, TNF-α, leptin, resistin, chemerin, fetuin-A, and other cytokines build an inflammatory and oxidative stress scenario from the polarization of macrophages M1 in adipose tissue, production of reactive oxygen species, decreased insulin action, and release of FFA in plasma.

    “Thus, myostatin, TNF-α, leptin, resistin, chemerin, fetuin-A, and other cytokines build an inflammatory and oxidative stress scenario from the polarization of macrophages (M ϕ) M1 in adipose tissue, production of reactive oxygen species, decreased insulin action, and release of FFA in plasma [11].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In obesity, leptin resistance caused by hyperleptinemia can limit muscle fatty acid oxidation and reduce lipolysis of adipose tissue.

    “In obesity, leptin resistance caused by hyperleptinemia can limit muscle fatty acid oxidation and reduce lipolysis of adipose tissue.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [99] Batsis, 2018, Sarcopenic obesity in older adults: Aetiology, epidemiology and treatment strategies, Nat. Rev. Endocrinol. source

      Not checked in the free run.

    • cites [100] Hirschfeld, 2017, Osteosarcopenia: Where bone, muscle, and fat collide, Osteopor. Int. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Myostatin levels are increased with physical inactivity and high levels of fat mass.

    “Present at the origin of several metabolic disorders, myostatin has negative effects on metabolism, and its levels are increased with physical inactivity and high levels of fat mass.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Deregulation of the secretion and production of adipokines and myokines contributes to excess adiposity and favors insulin resistance.

    “An important contribution to excess adiposity and favoring insulin resistance is the deregulation of the secretion and production of adipokines and myokines [96].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] Becerril, 2017, Crosstalk between adipokines and myokines in fat browning, Acta Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Myostatin promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines.

    “In parallel, myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity, which promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Oh, K.J., Lee, D.S., Kim, W.K., Han, B.S., Lee, S.C., and Bae, K.H. (2016). Metabolic adaptation in obesity and type II diabetes: Myokines, adipokines and hepatokines. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Disproportionate release of pro-inflammatory adipokines and reduction in lipolysis are simultaneous with insulin resistance, which plays a substantial role in the development of DM2.

    “Studies indicate that the disproportionate release of pro-inflammatory adipokines and the reduction in lipolysis are simultaneous with insulin resistance, which plays a substantial role in the development of DM2.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [104] Nayak, 2020, Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue, Physiol. Rep.

      Not checked in the free run.

    • cites [105] Goedeke, 2019, Emerging pharmacological targets for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes, Ann. Rev. Pharmacol. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tsukushi is an inducible hepatokine associated with the regulation of energy expenditure and is associated with obesity, NAFLD, and NASH.

    “Tsukushi representes an inducible hepatokine associated with the regulation of energy expenditure and is mightily associated with obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [78] Mouchiroud, 2019, The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis, JCI Insight source

      Not checked in the free run.

    • cites [88] Potthoff, 2021, Hepatokines and metabolism: Deciphering communication from the liver, Mol. Metab. source

      Not checked in the free run.

    • cites [89] Huang, 2021, Tsukushi is a novel prognostic biomarker and correlates with tumor-infiltrating B cells in non-small cell lung cancer, Aging source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hyperglycemia contributes to the production of advanced glycation end products (AGEs), which, together with reactive oxygen species, cause endothelial damage.

    “Hyperglycemia contributes to the production of advanced glycation end products (AGES), which, together with reactive oxygen species, cause endothelial damage, while adhesion molecules and immune cells are attracted to the vascular bed [94].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Castillo, 2020, Serum irisin levels, endothelial dysfunction, and inflammation in pediatric patients with type 2 diabetes mellitus and metabolic syndrome, J. Diab. Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines such as TNF-α, IL-1, resistin, chemerin, and others.

    “Thus, myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines such as TNF-α, IL-1, resistin, chemerin, and others [92].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Li, 2017, Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue, Cytokine Growth Factor Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adropin is considered a protective factor of the endothelium, which increases the synthesis of nitric oxide (NO) due to the activation of eNOS.

    “Therefore, adropin is considered a protective factor of the endothelium, which increases the synthesis of nitric oxide (NO) due to the activation of eNOS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The released organokines lead to numerous metabolic and physiological effects that can be harmful or beneficial to the body.

    “In this sense, the released organokines lead to numerous metabolic and physiological effects that can be harmful or beneficial to the body.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    They identified a less atherogenic apolipoprotein profile, reducing cardiovascular risks and promoting improvements in body weight and adiponectin levels.

    “It was also shown that they identified a less atherogenic apolipoprotein profile, reducing cardiovascular risks and promoting improvements in body weight and adiponectin levels [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In clinical studies, patients with DM2 treated with the FGF21 analog LY2405319 showed a reduction in LDL cholesterol and triglycerides, an increase in HDL cholesterol, and an improvement in insulin during fasting.

    “In clinical studies, patients who had DM 2 were treated with concentrations of FGF21 (with the analog LY2405319), and they showed a reduction in low-density lipoprotein (LDL) cholesterol and triglycerides, an increase in high-density lipoprotein (HDL) cholesterol, and an improvement in insulin during periods of fasting [75].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Ennequin, 2019, Role of exercise-induced hepatokines in metabolic disorders, Am. J. Physiol. Endocrinol. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FGF21 controls insulin sensitivity by improving fat oxidation in the muscle, de novo lipogenesis (DNL) in the liver, and thermogenesis in WAT and BAT.

    “FGF21 controls insulin sensitivity by improving fat oxidation in the muscle, de novo lipogenesis (DNL) in the liver, and thermogenesis in WAT and BAT.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [106] Degirolamo, 2016, Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23, Nat. Rev. Drug Disc. source

      Not checked in the free run.

    • cites [107] Keipert, 2020, Adapting to the cold: A role for endogenous fibroblast growth factor 21 in thermoregulation?, Front. Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FGF21, when working as a hepatokine, acts as a beta-oxidation regulator and decreases lipogenesis in the liver, especially when it increases in the post-exercise period.

    “In the same way that FGF21 is classified as myokine and adipokine, when working as an hepatokine, it acts as a beta-oxidation regulator and decreases lipogenesis in the liver, especially when it increases in the post-exercise period [11].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Obesity, insulin resistance, and inflammation are risk factors for several metabolic disorders.

    “It is well known that obesity, insulin resistance, and inflammation are risk factors for several metabolic disorders [108].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Lee, 2018, Obesity-induced insulin resistance and macrophage infiltration of the adipose tissue: A vicious cycle, J. Diabetes Investig. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The adipose, muscular, and hepatic tissues release several molecules that communicate through crosstalk and are capable of being biomarkers of homeostatic disorders.

    “The adipose, muscular, and hepatic tissues release several molecules that communicate through crosstalk and are capable of being biomarkers of homeostatic disorders, and they can play roles as potential therapeutic targets that can assist in methods of diagnosing, prognosis, and perhaps future treatments of metabolic syndrome and CVD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The release and complex interaction of these organokines depend on numerous factors, such as sedentary lifestyle and obesity.

    “The release and complex interaction of these organokines depend on numerous factors, such as the sedentary lifestyle and obesity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Plasma levels of adropin increase with physical training and culminate with the suppression of atherosclerosis due to the regulation of monocyte differentiation.

    “As a result, plasma levels of adropin increase with physical training and culminate with the suppression of atherosclerosis due to the regulation of monocyte differentiation, precisely its anti-inflammatory type.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Circulating follistatin is elevated in patients with DM2 and generally correlates with insulin resistance markers, such as fasting glucose, glycated hemoglobin, and 2-h glucose during an oral glucose tolerance test.

    “However, circulating follistatin was elevated in patients with DM2 and generally correlates with insulin resistance markers, such as fasting glucose, glycated hemoglobin, and 2-h glucose during an oral glucose tolerance test [111].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [111] Hansen, 2016, Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio, J. Clin. Endocrinol. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adropin levels decreased in patients with NASH and were negatively related to serum levels of alanine transaminase, aspartate aminotransferase, and gamma glutamyl transpeptidase.

    “On the other hand, a case–control study showed that adropin levels decreased in patients with NASH and were negatively related to serum levels of alanine transaminase, aspartate aminotransferase, and gamma glutamyl transpeptidase.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [113] Chen, X., Sun, X., Shen, T., Chen, Q., Chen, S., Pang, J., Mi, J., Tang, Y., You, Y., and Xu, H. (2020). Lower adropin expression is associated with oxidative stress and severity of nonalcoholic fatty liver disease. Free Radic. Biol. Med., 160. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Understanding how myokines, adipokines, and hepatokines interact can open up new paths in addressing metabolic problems, such as resistance to insulin and the development of diabetes, obesity, metabolic syndrome, and its repercussions.

    “The understanding of how myokines, adipokines, and hepatokines interact can open up new paths in addressing metabolic problems, such as resistance to the action of insulin and the development of diabetes, obesity, metabolic syndrome, and its countless repercussions in the body, such as cardiovascular diseases.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Adropin regulates plaque stability and vascular elasticity.

    “In this scenario, it was also observed that adropin increases fibronectin and elastin expression in vascular smooth muscle cells (VSMCs) by overloading the PI3K-Akt pathway, thus assuming that adropin regulates plaque stability and elasticity vascular [112].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fetuin-B negatively impacts metabolism because its serum level is higher in patients with coronary artery disease, especially in those with acute coronary syndrome.

    “Finally, fetuin-B also negatively impacts metabolism because its serum level is higher in patients with coronary artery disease, especially in those with the acute coronary syndrome, and it still positively correlates with LDL-c levels [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Zhu, 2017, Increased serum levels of fetuin B in patients with coronary artery disease, Endocrine source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adropin is expressed in endothelial cells and promotes proliferation, migration, formation of the capillary tube, attenuation of vascular permeability, and TNF-α-induced apoptosis.

    “It is expressed in endothelial cells and promotes essential functions, such as proliferation, migration, and formation of the capillary tube, together with attenuation of vascular permeability and TNF-α-induced apoptosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When activated by exercise, follistatin inactivates myostatin and inhibits its pro-inflammatory effects, cooperating with lipolysis in WAT.

    “When activated by exercise, follistatin inactivates myostatin and, therefore, inhibits its pro-inflammatory effects, consequently cooperating with lipolysis in WAT.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Gonzalez-Gil, A.M., and Elizondo-Montemayor, L. (2020). The role of exercise in the interplay between myokines, hepatokines, osteokines, adipokines, and modulation of inflammation for energy substrate redistribution and fat mass loss: A review. Nutrients, 12. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These hepatokines are usually elevated when associated with these pathologies and contribute to a state of systemic inflammation.

    “They are usually elevated when associated with these pathologies and contribute to a state of systemic inflammation [88].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Potthoff, 2021, Hepatokines and metabolism: Deciphering communication from the liver, Mol. Metab. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    These molecules can play roles as potential therapeutic targets that can assist in methods of diagnosing, prognosis, and perhaps future treatments of metabolic syndrome and CVD.

    “The adipose, muscular, and hepatic tissues release several molecules that communicate through crosstalk and are capable of being biomarkers of homeostatic disorders, and they can play roles as potential therapeutic targets that can assist in methods of diagnosing, prognosis, and perhaps future treatments of metabolic syndrome and CVD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Overweight individuals secrete more pro-inflammatory adipokines, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases.

    “Overweight individuals secrete more pro-inflammatory adipokines, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Soares, 2020, The role of adipokines in the Immunology of obesity, Res. Soc. Dev. source

      Not checked in the free run.

131 of 131

  • The paper relies on this without support.

    Adipose, skeletal muscle, and hepatic tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines.

    “Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines.”

  • The paper relies on this without support.

    These biomarkers can be harmful or beneficial and perform crosstalk through endocrine, paracrine, and autocrine pathways.

    “These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways.”

  • The paper relies on this without support.

    Many organokines are secreted by all three tissues.

    “Moreover, many organokines are secreted by all three tissues.”

  • The paper relies on this without support.

    No review has shown a comprehensive overview of crosstalk among these organokines with focus on insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease.

    “To the best of our knowledge, no review has shown a comprehensive overview of crosstalk or these organokines with focus on insulin resistance, diabetes, metabolic syndrome, and CVD.”

  • The paper relies on this without support.

    Overweight individuals secrete more pro-inflammatory adipokines than healthy-weight individuals, leading to impaired immune response and greater susceptibility to inflammatory and infectious diseases.

    “Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases.”

  • The paper relies on this without support.

    Myostatin is elevated in pro-inflammatory environments and co-occurs with pro-inflammatory organokines such as TNF-alpha, IL-1, resistin, and chemerin.

    “Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Fetuin-A induces a pro-inflammatory milieu by polarizing M1 macrophages in WAT, generating ROS and reducing insulin sensitivity, which combined with other pro-inflammatory cytokines causes the development of sarcopenia.

    “Fetuin-A, a systemic calcification inhibitor, induces a pro-inflammatory milieu by polarizing M1 macrophages in WAT, generating ROS and reducing insulin sensitivity, which combined with other pro-inflammatory cytokines causes the development of sarcopenia [122,123,124,125].”

    From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [124]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • FGF21 is said to both increase and decrease adipose-tissue lipolysis

    Minor

    The adipokine section attributes lipolysis to FGF21 in white adipose tissue, while the hepatokine section says FGF21 decreases lipolysis in adipose tissue. The text does not explain the opposing effects.

  • Pro-inflammatory organokines are listed as anti-inflammatory

    Minor

    The exercise section lists TNF-α, resistin, chemerin, and fetuin-A among anti-inflammatory organokines. Elsewhere, the paper describes these same substances as contributing to an inflammatory and oxidative-stress scenario.

2 of 2

Cites

Flagged first, then by citations

5 of the 120 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Sandhu, 2020, Cure of obesity in homeopathy: An approach to control a global epidemic, Tantian Univ. J. Homoeopath. Med. Sci., 1, 17
  2. Oliveira, 2019, Atualização da diretriz de prevenção cardiovascular da sociedade brasileira de cardiologia, Arq. Bras. Cardiol., 113, 787

Cited by

Sorted by citations

Related

Authors
de Oliveira dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., Mendes, C. G., Tofano, V. A. C., & dos Santos Haber, J. F.
Affiliations
  • Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho 1001, Marília 17525-902, São Paulo, Brazil
  • Universidade de Marília (BR)
  • Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenida Hygino Muzzy Filho 1001, Marília 17525-902, São Paulo, Brazil
  • Universidade de São Paulo (BR)
Corresponding author
Barbalho, Sandra Maria
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-03-05
Volume
22
Issue
5
Pages
2639
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22052639
PMC
PMC7961600
OpenAlex
W3133763745
Cited by
189
References
120
Citations by year
2026: 27 · 2025: 33 · 2024: 39 · 2023: 44 · 2022: 37 · 2021: 9
FWCI
4.94
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
adipokines, myokines, hepatokines, crosstalk, hormone signaling, paracrine signaling, autocrine signaling, type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, myostatin, FGF21, inflammatory cytokines, resistin, chemerin, TNF-α, interleukin-1, fatty acid beta-oxidation, lipogenesis, therapeutic target
MeSH terms
Animals, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Obesity, Cytokines, Metabolic Syndrome, Adipokines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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