Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“It acts on insulin sensitivity, and its plasma reduction is related to insulin resistance and glucose intolerance, predisposing to advanced liver injury [44].”

What the sources say

• Not checked yetcites [44] Buechler, C., Haberl, E.M., Rein-Fischboeck, L., and Aslanidis, C. (2017). Adipokines in liver cirrhosis. Int. J. Mol. Sci., 18. source

In the paper

“Adiponectin, an antisteatotic, anti-inflammatory, and antifibrotic adipokine, is expressed by adipocytes from WAT and brown adipose tissue (BAT).”

In the paper

“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).”

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [10] Faramia, 2020, Metabolic adaptations after bariatric surgery: Adipokines, myokines and hepatokines, Curr. Opin. Pharmacol. source
• Not checked yetcites [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 yetcites [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

In the paper

“Metreleptin is a recombinant methyl-human leptin hormone showing efficacy in children with congenital leptin deficiency reversal of obesity and metabolic improvement [42].”

What the sources say

• Not checked yetcites [42] Farooqi, 1999, Effects of recombinant leptin therapy in a child with congenital leptin deficiency, N. Engl. J. Med. source

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [40] Merli, 2019, Sarcopenic obesity in fatty liver, Curr. Opin. Clin. Nutr. Metab. Care source

In the paper

“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).”

In the paper

“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].”

What the sources say

• Not checked yetcites [12] Lund, 2020, Leptin, adiponectin, and their ratio as markers of insulin resistance and cardiometabolic risk in childhood obesity, Pediatr. Diab. source

In the paper

“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].”

What the sources say

• Not checked yetcites [19] Watanabe, 2017, Adipose tissue-derived omentin-1 function and regulation, Compr. Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [16] Duerrschmid, 2017, Asprosin is a centrally acting orexigenic hormone, Nat. Med. source
• Not checked yetcites [17] Romere, 2016, Asprosin, a fasting-induced glucogenic protein hormone, Cell source

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [20] Mehta, 2019, Fibroblast growth factor 21 and browning of white adipose tissue, Front. Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

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

In the paper

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

In the paper

“However, the function of vaspin is to improve glucose intolerance and insulin sensitivity and reduce the synthesis of pro-inflammatory cytokines [24].”

What the sources say

• Not checked yetcites [24] Kukla, 2020, Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma, Clin. Exp. Hepatol. source

In the paper

“Its action occurs through several receptors, including adipoR1 and adipoR2.”

In the paper

“Asprosin, which is encoded by the FBN1 locus, has a role in the mediation of the lipodystrophy phenotype [48].”

What the sources say

• Not checked yetcites [48] Lin, 2020, Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1, Mol. Genet. Genom. Med. source

In the paper

“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].”

What the sources say

• Not checked yetcites [45] Mikolasevic, 2020, Nonalcoholic fatty liver disease and sarcopenia: Where do we stand?, Can. J. Gastroenterol. Hepatol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [49] Kim, 2020, Newly discovered adipokines: Pathophysiological link between obesity and cardiometabolic disorders, Front. Physiol. source

In the paper

“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.”

In the paper

“In turn, omentin acts to improve insulin sensitivity and glucose absorption and acts as an anti-atherosclerotic factor.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [46] Fang, 2018, Adiponectin regulation and function, Comprehensive Physiology source

In the paper

“In humans, FGF21 is responsible for the browning of WAT, activation of brown adipocytes, and lipolysis.”

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [18] Shi, 2019, Cytokines and abnormal glucose and lipid metabolism, Front. Endocrinol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [28] Lei, 2017, C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance, J. Biol. Chem. source

In the paper

“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].”

What the sources say

• Not checked yetcites [15] Musovic, 2020, Resistin is co-secreted with adiponectin in white mouse adipocytes, Biochem. Biophys. Res. Commun. source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [23] Recinella, 2020, Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases, Front. Physiol. source

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

In the paper

“Each myokine appears to be related to a specific type of muscle fiber and different physical exercise modalities [56] (Table 2).”

What the sources say

• Not checked yetcites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

In the paper

“Therefore, induction of adipocyte browning by irisin suppresses adipogenesis and cholesterol synthesis and optimizes lipid oxidation and lipidic homeostasis by extension.”

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [57] Mikolajczak, 2017, Serum FGF21 in girls with anorexia nervosa—Comparison to normal weight and obese female adolescents, Neuro Endocrinol. Lett.

In the paper

“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.”

In the paper

“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.”

In the paper

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

In the paper

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

In the paper

“Its secretion is more significant in the subcutaneous adipose tissue and is associated with an enzymatic activity such as nicotinamide phosphoribosyltransferase (NAMPT) [33].”

What the sources say

• Not checked yetcites [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

In the paper

“Studies point to a relationship between high levels of irisin and low atherosclerosis burden in coronary arteries, proving its cardioprotective effects [8].”

What the sources say

• Not checked yetcites [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

In the paper

“Thus, follistatin contributes to the increase in muscle mass, optimizing glucose uptake by SkM and WAT lipolysis [11,13].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“Possibly, myostatin inhibition may be a therapeutic target for muscle mass loss disorders, such as atrophy, sarcopenia, and cancer [45].”

What the sources say

• Not checked yetcites [45] Mikolasevic, 2020, Nonalcoholic fatty liver disease and sarcopenia: Where do we stand?, Can. J. Gastroenterol. Hepatol. source

In the paper

“It increases insulin sensitivity, reduces plasma glucose levels, and has lipolytic activity, which decreases plasma triglyceride levels [10].”

What the sources say

• Not checked yetcites [10] Faramia, 2020, Metabolic adaptations after bariatric surgery: Adipokines, myokines and hepatokines, Curr. Opin. Pharmacol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [20] Mehta, 2019, Fibroblast growth factor 21 and browning of white adipose tissue, Front. Physiol. source

In the paper

“Additionally, it helps in the reduction in visceral adipose tissue without reducing subcutaneous fat, showing performance in muscle-fat crosstalk [14].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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.”

In the paper

“Visfatin in high concentrations causes insulin resistance and pancreatic beta-cell dysfunction and produces inflammation in adipocytes [34].”

What the sources say

• Not checked yetcites [34] Kumari, 2018, Adipokine visfatin’s role in pathogenesis of diabesity and related metabolic derangements, Curr. Mol. Med. source

In the paper

“Moreover, some experimental studies point to a possible correlation between increased levels of IL-6 and inhibition of appetite [52].”

What the sources say

• Not checked yetcites [52] Yuan, 2020, Asprosin: A novel player in metabolic diseases, Front. Endocrinol. source

In the paper

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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [18] Shi, 2019, Cytokines and abnormal glucose and lipid metabolism, Front. Endocrinol. source

In the paper

“Fibroblast growth factor 21 (FGF21) is produced by several tissues classified as myokine, adipokines, and hepatokine.”

In the paper

“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 the paper

“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.”

In the paper

“On the other hand, the adipokine zinc-α2-glycoprotein (ZAG) is expressed by both white and BAT and directly accelerates lipid metabolism [38].”

What the sources say

• Not checked yetcites [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

In the paper

“This myokine shows positive effects on the cardiovascular system, which may reveal a potential therapeutic target in CVD treatment [8].”

What the sources say

• Not checked yetcites [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

In the paper

“In addition, nesfatin-1 can regulate gastric distension and motility via the melanocortin pathway in the central nucleus of the amygdala [23].”

What the sources say

• Not checked yetcites [23] Recinella, 2020, Adipokines: New potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases, Front. Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [31] Abella, 2017, Leptin in the interplay of inflammation, metabolism and immune system disorders, Nat Rev. Rheumatol. source
• Not checked yetcites [32] Korolczuk, 2017, Progranulin, a new adipokine at the crossroads of metabolic syndrome, diabetes, dyslipidemia and hypertension, Curr. Pharm. Design source

In the paper

“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].”

What the sources say

• Not checked yetcites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

In the paper

“Hepatokines are proteins produced by the liver that have recently been discovered as new hormones, which can worsen or improve metabolic conditions [64].”

What the sources say

• Not checked yetcites [64] Choi, 2016, The impact of organokines on insulin resistance, inflammation, and atherosclerosis, Endocrinol. Metab. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“Studies have shown that in mice, plasma levels of adropin increase with feeding and decrease with fasting.”

In the paper

“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].”

What the sources say

• Not checked yetcites [79] Iroz, 2015, Hepatokines: Unlocking the multi-organ network in metabolic diseases, Diabetologia source

In the paper

“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].”

What the sources say

• Not checked yetcites [60] Aoi, 2019, Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation, FASEB J. source

In the paper

“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].”

What the sources say

• Not checked yetcites [61] Cooper, 2018, On the run for hippocampal plasticity, Cold Spring Harbor Perspect. Med. source

In the paper

“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].”

What the sources say

• Not checked yetcites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

In the paper

“Besides that, it is also related to glucose and lipid metabolism regulation and increased insulin sensitivity when released by muscle [14].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [56] Barbalho, 2020, Myokines: A descriptive review, J. Sports Med. Phys. Fitness source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [81] Zhao, 2015, Serum adropin level in patients with stable coronary artery disease, Heart Lung Circulat. source

In the paper

“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].”

What the sources say

• Not checked yetcites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

In the paper

“It is also able to inhibit the formation of adipose tissue, increase the release of insulin and promote erythropoiesis [14].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [75] Ennequin, 2019, Role of exercise-induced hepatokines in metabolic disorders, Am. J. Physiol. Endocrinol. Metab. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [74] Perakakis, 2018, Physiology of activins/follistatins: Associations with metabolic and anthropometric variables and response to exercise, J. Clin. Endocrinol. Metab. source

In the paper

“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.”

What the sources say

• Not checked yetcites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

In the paper

“However, in humans, activin E has been reported to reduce lipolysis and increase fat accumulation in adipocytes.”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [97] Makowski, 2020, Chapter four—Myokines: The endocrine coupling of skeletal muscle and bone, Advances in Clinical Chemistry source

In the paper

“ANGPTL6 is highly expressed in obesity, augmented lipid accumulation in skeletal muscle and liver, reduced energy expenditure, and increased insulin resistance.”

In the paper

“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].”

What the sources say

• Not checked yetcites [104] Nayak, 2020, Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue, Physiol. Rep.
• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [102] Gannar, 2018, Myokines, physical activity, insulin resistance and autoimmune diseases, Immunol. Lett. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

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

What the sources say

• Not checked yetcites [99] Batsis, 2018, Sarcopenic obesity in older adults: Aetiology, epidemiology and treatment strategies, Nat. Rev. Endocrinol. source
• Not checked yetcites [100] Hirschfeld, 2017, Osteosarcopenia: Where bone, muscle, and fat collide, Osteopor. Int. source

In the paper

“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.”

In the paper

“An important contribution to excess adiposity and favoring insulin resistance is the deregulation of the secretion and production of adipokines and myokines [96].”

What the sources say

• Not checked yetcites [96] Becerril, 2017, Crosstalk between adipokines and myokines in fat browning, Acta Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [104] Nayak, 2020, Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue, Physiol. Rep.
• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [78] Mouchiroud, 2019, The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis, JCI Insight source
• Not checked yetcites [88] Potthoff, 2021, Hepatokines and metabolism: Deciphering communication from the liver, Mol. Metab. source
• Not checked yetcites [89] Huang, 2021, Tsukushi is a novel prognostic biomarker and correlates with tumor-infiltrating B cells in non-small cell lung cancer, Aging source

In the paper

“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].”

What the sources say

• Not checked yetcites [94] Castillo, 2020, Serum irisin levels, endothelial dysfunction, and inflammation in pediatric patients with type 2 diabetes mellitus and metabolic syndrome, J. Diab. Res.

In the paper

“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].”

What the sources say

• Not checked yetcites [92] Li, 2017, Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue, Cytokine Growth Factor Rev. source

In the paper

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

What the sources say

• Not checked yetcites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [67] Meex, 2017, Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance, Nat. Rev. Endocrinol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [75] Ennequin, 2019, Role of exercise-induced hepatokines in metabolic disorders, Am. J. Physiol. Endocrinol. Metab. source

In the paper

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

What the sources say

• Not checked yetcites [106] Degirolamo, 2016, Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23, Nat. Rev. Drug Disc. source
• Not checked yetcites [107] Keipert, 2020, Adapting to the cold: A role for endogenous fibroblast growth factor 21 in thermoregulation?, Front. Endocrinol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“It is well known that obesity, insulin resistance, and inflammation are risk factors for several metabolic disorders [108].”

What the sources say

• Not checked yetcites [108] Lee, 2018, Obesity-induced insulin resistance and macrophage infiltration of the adipose tissue: A vicious cycle, J. Diabetes Investig. source

In the paper

“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.”

In the paper

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

In the paper

“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.”

What the sources say

• Not checked yetcites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [111] Hansen, 2016, Circulating follistatin is liver-derived and regulated by the glucagon-to-insulin ratio, J. Clin. Endocrinol. Metab. source

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

In the paper

“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].”

What the sources say

• Not checked yetcites [114] Zhu, 2017, Increased serum levels of fetuin B in patients with coronary artery disease, Endocrine source

In the paper

“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.”

What the sources say

• Not checked yetcites [112] Mushala, 2021, Adropin: A hepatokine modulator of vascular function and cardiac fuel metabolism, Am. J. Physiol. Circ. Physiol. source

In the paper

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

What the sources say

• Not checked yetcites [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

In the paper

“They are usually elevated when associated with these pathologies and contribute to a state of systemic inflammation [88].”

What the sources say

• Not checked yetcites [88] Potthoff, 2021, Hepatokines and metabolism: Deciphering communication from the liver, Mol. Metab. source

In the paper

“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.”

In the paper

“Overweight individuals secrete more pro-inflammatory adipokines, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases [109].”

What the sources say

• Not checked yetcites [109] Soares, 2020, The role of adipokines in the Immunology of obesity, Res. Soc. Dev. source