Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

In the paper

“Elevated levels of leptin were associated with development, progression and prognostication of non-alcoholic fatty liver disease (NAFLD) [41].”

What the sources say

• Not checked yetcites [41] Polyzos, 2016, Circulating leptin in non-alcoholic fatty liver disease: A systematic review and meta-analysis, Diabetology source

In the paper

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

What the sources say

• Not checked yetcites [43] Moon, 2011, Efficacy of metreleptin in obese patients with type 2 diabetes: Cellular and molecular pathways underlying leptin tolerance, Diabetes source

In the paper

“Leptin is released by subcutaneous white adipose tissue (WAT) [39]”

What the sources say

• Not checked yetcites [39] Scheja, 2019, The endocrine function of adipose tissues in health and cardiometabolic disease, Nat. Rev. Endocrinol. source

In the paper

“Therefore, they have specific associations with insulin resistance, diabetes mellitus, obesity, metabolic syndrome, and CVD [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

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

“The excess weight combined with hyperglycemia predisposes oxidative stress and inflammation [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

“High levels of LCN2 are associated with CVD, vascular remodeling, and instability of atherosclerotic plaques by regulating the metalloproteinase activity (MMP-9) [22].”

What the sources say

• Not checked yetcites [22] Cakirca, 2018, Serum matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9/ neutrophil gelatinase-associated lipocalin complex levels in patients with early-stage diabetic nephropathy, Iran. J. Kidney Dis.

In the paper

“Lipocalin 2 (LCN2), also associated with neutrophil gelatinase-associated lipocalin (NGAL), is a glycoprotein identified as the cytokine of adipose tissue present in low-level systemic inflammation in obese patients with metabolic syndrome.”

In the paper

“Therefore, the inhibition of adipogenesis can restrict the storage of triglycerides in tissue adipose, increasing circulating levels (systemic hyperlipidemia) and lipid deposition in the liver and skeletal muscle [55].”

What the sources say

• Not checked yetcites [55] Fu, 2018, Circulating osteonectin and adipokine profiles in relation to metabolically healthy obesity in Chinese children: Findings from BCAMS, J. Am. Heart Assoc. source

In the paper

“These protective actions of asprosin can be associated to its functions of enhancing mitochondrial respiration under hypoxia [51].”

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

“The secreted acidic protein rich in cysteine (SPARC), known as BM40 or osteonectin, modulates the expression of pro-inflammatory cytokines involved in insulin resistance and adipogenesis [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

“Studies show that vaspin protects vascular tissues from fatty acid-induced apoptosis via the signaling pathway PI3K/Akt/eNOS [25].”

What the sources say

• Not checked yetcites [25] Zieger, 2018, Vaspin suppresses cytokine-induced inflammation in 3T3-L1 adipocytes via inhibition of NFκB pathway, Mol. Cell. Endocrinol. source

In the paper

“In humans, it is produced by macrophages and monocytes infiltrated in adipose tissue.”

In the paper

“Another substance recently introduced as an adipokine is fibroblast growth factor 21 (FGF21), whose exposure to cold or physical exercise causes its expression in white and BAT.”

In the paper

“Its receptors, the megalin/glycoprotein GP330 and SLC22A17 or 24p3R, the solute carrier family 22 members 17 binding mouse LCN2, are involved in regulating inflammation and the transport of fatty acids and iron [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

“Recently, an orally active synthetic adiponectin receptor agonist, AdipoRon, was developed and studied in an experimental animal study (mice) showing improvement in vascular function in the mesenteric arteries independently of endothelium-mechanism [47].”

What the sources say

• Not checked yetcites [47] Choi, S.-K., Kwon, Y., Byeon, S., Haam, C.E., and Lee, Y.-H. (2020). AdipoRon, adiponectin receptor agonist, improves vascular function in the mesenteric arteries of type 2 diabetic mice. PLoS ONE, 15. source

In the paper

“For these reasons, asprosin can be an important biomarker for predicting the development of diabetes.”

What the sources say

• Not checked yetcites [50] Gozel, N., and Kilinc, F. (2020). Investigation of plasma asprosin and saliva levels in newly diagnosed type 2 diabetes mellitus patients treated with metformin. Endokrynol. Polska. source

In the paper

“The secreted frizzled-related protein 5 (SFRP5), recently identified as an adipokine, is expressed in WAT in higher amounts compared to other tissues.”

In the paper

“Asprosin levels are elevated in comorbidities such as obesity and DM2.”

In the paper

“In glucose metabolism, resistin is related to activating an inhibitor of insulin signaling, the suppressor of cytokine signaling 3 (SOCS3).”

In the paper

“It can also suppress vascular cell proliferation and migration by reducing the c-Jun N-terminal kinase (JNK) and ERK1/2 pathways and increasing collagen via the PI3K/Akt pathways [54].”

What the sources say

• Not checked yetcites [54] Sato, K., Shirai, R., Yamaguchi, M., Yamashita, T., Shibata, K., Okano, T., Mori, Y., Matsuyama, T.A., Ishibashi-Ueda, H., and Hirano, T. (2018). Anti-atherogenic effects of vaspin on human aortic smooth muscle cell/macrophage responses and hyperlipidemic mouse plaque phenotype. Int. J. Mol. Sci., 19. source

In the paper

“Its function is related to the inhibition in the initial stage of adipogenesis through inhibiting the mitotic clonal expansion of pre-adipocytes [27].”

What the sources say

• Not checked yetcites [27] Mukherjee, 2020, Secreted protein acidic and rich in cysteine (SPARC) regulates thermogenesis in white and brown adipocytes, Mol. Cell. Endocrinol. source

In the paper

“Studies demonstrate that FAM19A5 inhibits vascular smooth muscle cell proliferation and inflammation related to cardiovascular disease through obesity [29].”

What the sources say

• Not checked yetcites [29] Zarzour, 2018, Understanding obesity-related cardiovascular disease: It’s all about balance, Circulation source

In the paper

“The decrease in plasma apelin is commonly observed in the elderly due to the reduction in muscle mass.”

In the paper

“Irisin, one of the most recent myokines identified, is a cleavage product of type III transmembrane fibronectin protein containing domain 5 (FNDC5), released after cleavage of the carboxy group.”

In the paper

“It has great therapeutic potential in several metabolic comorbidities, such as obesity, DM2, and metabolic syndrome.”

In the paper

“Unlike most myokines, exercise seems to decrease myostatin expression.”

In the paper

“It also stimulates insulin release by increasing the expression of the glucagon-1-like peptide (GLP-1) [11,59].”

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 [59] Chung, 2020, Organokines in disease, Adv. Clin. Chem. source

In the paper

“Elevated levels of FGF21 after exercise reveal crucial functions for glucose and lipid metabolism.”

In the paper

“Fet-A levels are increased in obese individuals with diabetes [35].”

What the sources say

• Not checked yetcites [35] Khadir, 2020, Fetuin-a expression profile in mouse and human adipose tissue, Lip. Health Dis. source

In the paper

“Therefore, this myokine is also pointed out as a biomarker of early sarcopenia [58].”

What the sources say

• Not checked yetcites [58] Kwon, J.H., Moon, K.M., and Min, K.W. (2020). Exercise-induced myokines can explain the importance of physical activity in the elderly: An overview. Healthcare, 8. source

In the paper

“Myostatin exhibits negative consequences when it is at increased levels, as it acts as a facilitator of muscle mass loss, either by inhibiting factors that promote tissue growth or by stimulating degradation mechanisms.”

In the paper

“Studies show that serum ZAG levels are lower in overweight or obese patients [37].”

What the sources say

• Not checked yetcites [37] Wang, 2020, Low serum ZAG levels correlate with determinants of the metabolic syndrome in Chinese subjects, Front. Endocrinol. source

In the paper

“Experimental studies of visceral obesity have found that WISP1 can induce mesenchymal stem cells’ proliferation and, consequently, the expansion of tissue adipose [30].”

What the sources say

• Not checked yetcites [30] Barchetta, 2017, WISP1 is a marker of systemic and adipose tissue inflammation in dysmetabolic subjects with or without type 2 diabetes, J. Endocr. Soc. source

In the paper

“This myokine has been shown to contribute to the browning of WAT and, consequently, to greater energy expenditure through the oxidation of glucose and FFA and reduction in fat mass [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

“A study in mice showed that activin E has several functions: initially, it is needed to induce thermogenesis by stimulating beige adipocytes in WAT; then, its overexpression raises thermogenesis and insulin sensitivity by stimulating activity of brown adipocytes in BAT; finally, activin E is closely related to FGF21 in WAT, which may increase its expression in brown pre-adipocyte culture.”

What the sources say

• Not checked yetcites [68] Hashimoto, 2018, Activin E controls energy homeostasis in both brown and white adipose tissues as a hepatokine, Cell Rep. source

In the paper

“Thus, it ended up providing evidence that adropin affected the progression of vascular atherosclerosis [81].”

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

“A study in mice showed that activin E has several functions: initially, it is needed to induce thermogenesis by stimulating beige adipocytes in WAT; then, its overexpression raises thermogenesis and insulin sensitivity by stimulating activity of brown adipocytes in BAT; finally, activin E is closely related to FGF21 in WAT, which may increase its expression in brown pre-adipocyte culture.”

What the sources say

• Not checked yetcites [68] Hashimoto, 2018, Activin E controls energy homeostasis in both brown and white adipose tissues as a hepatokine, Cell Rep. source

In the paper

“METRNL also shows an anti-inflammatory role, especially in reducing adipose inflammation, increasing the expression of M2 macrophages in adipose tissue, and improving insulin resistance typical of obesity [62].”

What the sources say

• Not checked yetcites [62] Gholamrezayi, 2020, Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines, Lip. Health Dis. source

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

“As a result, these low levels are observed in people with obesity, polycystic ovary syndrome, fatty liver, insulin resistance, and CVD, suggesting that low levels of adropin are closely associated with metabolic disorders.”

In the paper

“On the other hand, the decrease in fetuin-A levels by physical activity can show a beneficial potential by reducing visceral adipose tissue via a reduction in the available FFA.”

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

“Fetuin-A performs deleterious functions in these metabolic diseases precisely because it can develop injury to pancreatic β cells, which are responsible for insulin production [65].”

What the sources say

• Not checked yetcites [65] Shen, 2015, Fetuin A promotes lipotoxicity in β cells through the TLR4 signaling pathway and the role of pioglitazone in anti-lipotoxicity, Mol. Cell. Endocrinol. source

In the paper

“A study of patients who underwent bariatric surgery showed that weight loss increased levels of adropin [80].”

What the sources say

• Not checked yetcites [80] Rogala, 2019, Serum irisin, adropin, and preptin in obese patients 6 months after bariatric surgery, Obesity Surg. 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

“Meteorin-like protein (METRNL) is also positively regulated after resistance exercises, performing a series of beneficial actions for the metabolism of different tissues.”

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 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

“In humans, plasma levels of fetuin-B are elevated in obese people with fatty liver and DM2, and studies have shown that steatosis is more closely related to the development of insulin resistance than obesity itself.”

What the sources say

• Not checked yetcites [66] Ruth, 2015, Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism, Cell Metab. source

In the paper

“Indeed, it has been shown that fetuin-B decreases insulin sensitivity in muscle and hepatocytes in culture when administered to them in physiological concentrations, and, in this situation, it was not able to activate pro-inflammatory signaling [66].”

What the sources say

• Not checked yetcites [66] Ruth, 2015, Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism, Cell Metab. source

In the paper

“Such situations are regulated via autocrine, paracrine, and endocrine both in the liver and other tissues [18].”

What the sources say

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

In the paper

“This myokine has been shown to contribute to the browning of WAT and, consequently, to greater energy expenditure through the oxidation of glucose and FFA and reduction in fat mass [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

“Thus, fetuin B can promote insulin resistance in myotubes and hepatocytes [18].”

What the sources say

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

In the paper

“Thus, it is still noteworthy that the reduction in fetuin-A levels can control the accumulation of visceral adipose tissue by decreasing the activation of macrophage 1, which has a pro-inflammatory action [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

“A recent study of patients undergoing coronary artery bypass graft surgery showed that the lowest level of plasma adropin was associated with late saphenous vein graft occlusion.”

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

“Adropin is a small peptide whose concentrations are immediately regulated by the energy status and nutritional content of the diet.”

In the paper

“Even so, there is a greater interference of hepatokines in the fatty and striated skeletal muscle tissue, showing an endocrine-dependent relationship, therefore acting through crosstalk with the cytokines released by these respective tissues [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

“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

“This myokine has been shown to contribute to the browning of WAT and, consequently, to greater energy expenditure through the oxidation of glucose and FFA and reduction in fat mass [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

“Like fetuin-A, fetuin B is the second member of the fetuin family, produced primarily by the liver and acts by inhibiting the tyrosine kinase insulin receptor.”

What the sources say

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

In the paper

“METRNL also shows an anti-inflammatory role, especially in reducing adipose inflammation, increasing the expression of M2 macrophages in adipose tissue, and improving insulin resistance typical of obesity [62].”

What the sources say

• Not checked yetcites [62] Gholamrezayi, 2020, Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines, Lip. Health Dis. source

In the paper

“METRNL also shows an anti-inflammatory role, especially in reducing adipose inflammation, increasing the expression of M2 macrophages in adipose tissue, and improving insulin resistance typical of obesity [62].”

What the sources say

• Not checked yetcites [62] Gholamrezayi, 2020, Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines, Lip. Health Dis. source

In the paper

“In humans, plasma levels of fetuin-B are elevated in obese people with fatty liver and DM2, and studies have shown that steatosis is more closely related to the development of insulin resistance than obesity itself.”

What the sources say

• Not checked yetcites [66] Ruth, 2015, Fetuin B is a secreted hepatocyte factor linking steatosis to impaired glucose metabolism, Cell Metab. source

In the paper

“Therefore, this liver cytokine plays a deleterious role when at high levels in patients with pre-diabetes and DM2, causing insulin resistance and hyperglycemia [73].”

What the sources say

• Not checked yetcites [73] Misu, 2017, Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle, Nat. Med. source

In the paper

“Beyond that, studies in rats, monkeys, and humans have shown that FGF21 moderates simple sugar intake and preferences for sweet foods via signaling with FGF21 receptors in the paraventricular nucleus of the hypothalamus and correlates with decreased dopamine neurotransmission within the nucleus accumbens [84].”

What the sources say

• Not checked yetcites [84] Pedersen, 2019, Physical activity and muscle-brain crosstalk, Nat. Rev. Endocrinol. source

In the paper

“It has been found that the Paigen diet is associated with nonalcoholic fatty liver disease due to the high cholesterol content that promotes liver chemerin expression.”

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

“Obese rats submitted to a diet-induced weight cycling demonstrated a high hepatic production of LECT2 [87].”

What the sources say

• Not checked yetcites [87] Chikamoto, 2016, Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice, Biochem. Biophys. Res. Commun. source

In the paper

“At first, an association of this pathology with a low serum level of SHBG was found in post-menopausal women with NAFLD [70].”

What the sources say

• Not checked yetcites [70] Lebensztejn, 2016, Hepatokines and non-alcoholic fatty liver disease, Acta Biochim. Polonica source

In the paper

“However, it has been shown that in humans, serum levels of hepassocin are elevated in pre-diabetes, DM2, and NAFLD because of their association with impaired fasting glucose, glucose intolerance, and insulin resistance [77].”

What the sources say

• Not checked yetcites [77] Wu, 2016, A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes, Diabetologia source

In the paper

“However, the increase in serum ANGPTL4 may be related to insulin resistance in patients with metabolic syndrome compared to normal patients [70].”

What the sources say

• Not checked yetcites [70] Lebensztejn, 2016, Hepatokines and non-alcoholic fatty liver disease, Acta Biochim. Polonica source

In the paper

“Initially, it acts on insulin sensitization, increases the oxidation of fatty acids in the liver, decreases the production of glucose, increases the turnover of FFA, and reduces the development of steatohepatitis.”

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

In the paper

“Initially, it acts on insulin sensitization, increases the oxidation of fatty acids in the liver, decreases the production of glucose, increases the turnover of FFA, and reduces the development of steatohepatitis.”

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

In the paper

“As suggested previously, in the adipose tissue, FGF21 decreases lipolysis in vivo and in vitro, incites glucose retention in human adipocytes by inducing the expression of GLUT1 (which in fact improves insulin sensitivity in adipose tissue), increases expression and production of adiponectin, and “darkens” the white adipose tissue, turning it into brown.”

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

In the paper

“Patients with obesity-related to insulin resistance show an increase in the basal levels of follistatin.”

In the paper

“As suggested previously, in the adipose tissue, FGF21 decreases lipolysis in vivo and in vitro, incites glucose retention in human adipocytes by inducing the expression of GLUT1 (which in fact improves insulin sensitivity in adipose tissue), increases expression and production of adiponectin, and “darkens” the white adipose tissue, turning it into brown.”

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

In the paper

“As suggested previously, in the adipose tissue, FGF21 decreases lipolysis in vivo and in vitro, incites glucose retention in human adipocytes by inducing the expression of GLUT1 (which in fact improves insulin sensitivity in adipose tissue), increases expression and production of adiponectin, and “darkens” the white adipose tissue, turning it into brown.”

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

In the paper

“High levels of chemerin are detected in obesity, metabolic syndrome, insulin resistance, and dyslipidemia [72].”

What the sources say

• Not checked yetcites [72] Pohl, 2017, Hepatic chemerin mRNA expression is reduced in human nonalcoholic steatohepatitis, Eur. J. Clin. Investig. source

In the paper

“Angiopoietin-like 4 (ANGPTL4) is released by the liver into the circulation, especially during physical exercise because of the increased glucagon/insulin ratio, and it inhibits pancreatic lipases, which consequently decreases the absorption of fats [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

“Angiopoietin-like 4 (ANGPTL4) is released by the liver into the circulation, especially during physical exercise because of the increased glucagon/insulin ratio, and it inhibits pancreatic lipases, which consequently decreases the absorption of fats [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, this low concentration has also been identified in DM2 and obese patients.”

In the paper

“Initially, it acts on insulin sensitization, increases the oxidation of fatty acids in the liver, decreases the production of glucose, increases the turnover of FFA, and reduces the development of steatohepatitis.”

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.
• 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 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

“It is inferred that activin E may be a therapeutic target for obesity [68].”

What the sources say

• Not checked yetcites [68] Hashimoto, 2018, Activin E controls energy homeostasis in both brown and white adipose tissues as a hepatokine, Cell Rep. source

In the paper

“Follistatin is able to contribute to skeletal muscle fiber hypertrophy due to its affinity for myostatin, neutralizing it and increasing skeletal muscle mass, and inducing the expression of thermogenic genes in murine adipocytes.”

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

“However, after exercise, the increase in follistatin levels is beneficial since it favors successive glucose uptake by skeletal muscle tissue [83].”

What the sources say

• Not checked yetcites [83] Weigert, 2019, Hepatokines—A novel group of exercise factors, Eur. J. Physiol. source

In the paper

“It was recently found that adiponectin increases the production of SHBG by activating AMPK and reducing the activity of enzymes involved in liver lipogenesis.”

What the sources say

• Not checked yetcites [71] Selva, 2015, Novel insights in SHBG regulation and clinical implications, Trends Endocrinol. Metab. source

In the paper

“Initially, it acts on insulin sensitization, increases the oxidation of fatty acids in the liver, decreases the production of glucose, increases the turnover of FFA, and reduces the development of steatohepatitis.”

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

In the paper

“That is, chemerin hyperexpression is found in patients with NAFLD and nonalcoholic steatohepatitis [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

“As suggested previously, in the adipose tissue, FGF21 decreases lipolysis in vivo and in vitro, incites glucose retention in human adipocytes by inducing the expression of GLUT1 (which in fact improves insulin sensitivity in adipose tissue), increases expression and production of adiponectin, and “darkens” the white adipose tissue, turning it into brown.”

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

In the paper

“Therefore, LECT2 can be an important marker to explain how the fatty liver leads to insulin resistance in obesity since its deletion of LECT2 increases insulin sensitivity in skeletal muscle in rats [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

“Far beyond understanding each adipokine, myokine, or hepatokine’s actions alone, it is important to underline that these cytokines act together in the body, forming 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 DM2, obesity, metabolic syndrome, and CVD”

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

“Adipo-myokines, such as IL-6 and TNF-α, secreted from muscle cells and adipocytes, if chronically elevated, can induce insulin resistance and consequently other comorbidities [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

“For these reasons, physical exercise is a powerful ally in the prevention and improvement of the prognosis of cardiovascular diseases, DM2, and obesity, since it influences the predominance of the secretion of anti-inflammatory myokines, adipokines, and hepatokines, such as irisin, IL-6, IL -15, myonectin, adiponectin, FGF21 (which mitigate the harmful effects of myostatin), TNF-α, resistin, cheme”

What the sources say

• Not checked yetcites [101] Chen, 2020, Myokines mediate the cross talk between skeletal muscle and other organs, J. Cell. Physiol. source

In the paper

“Hepatic and plasma levels of this hepatokine are strongly stimulated by stimuli that augment thermogenesis and energy expenditure (including adrenergic agonists and cold exposure) [78,88,89].”

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

“These cytokines, especially TNF-α and leptin, seem to aggravate hypertension, which, together with visceral obesity, dyslipidemia, and hyperglycemia, configure the metabolic syndrome scenario [59,93].”

What the sources say

• Not checked yetcites [59] Chung, 2020, Organokines in disease, Adv. Clin. Chem. source
• Not checked yetcites [93] Chen, 2019, The role of myokines and adipokines in hypertension and hypertension-related complications, Hypertens. Res. source

In the paper

“In obese and diabetic individuals, visceral fat is related to the expression of IL-6 and TNF-α produced by macrophages that prevent or attenuate insulin signaling in insulin-dependent tissues.”

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

“Therefore, it is worth noting that myostatin has a role as a therapeutic target for managing these aforementioned metabolic disorders [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

“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

“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

“Beyond that, these cytokines appear to exhibit a protective effect on the endothelium and vascular smooth muscle, preventing atherosclerosis [103].”

What the sources say

• Not checked yetcites [103] Byun, K., and Lee, S. (2020). The potential role of irisin in vascular function and atherosclerosis: A review. Int. J. Mol. Sci., 21. source

In the paper

“Its contribution to resistance to the action of insulin occurs due to the decrease in phosphorylation of insulin receptor, compromising the entire insulin signaling pathway necessary to trigger its cellular actions [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

“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

“Therefore, hepassocin can be a relevant biomarker for analyzing risk states for diabetes and may be known by other names, such as fibrinogen-like protein 1 and hepatocyte-derived fibrinogen-related protein 1 (HFREP1) [18].”

What the sources say

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

In the paper

“In muscle aging, increased plasma levels of IL-6 and TNF-α, associated with loss of muscle strength, activate cell signaling pathways that lead to skeletal muscle atrophy, which in turn induce resistance to IL-6, a condition that shares similarities with insulin or leptin resistance [98].”

What the sources say

• Not checked yetcites [98] Kirk, 2020, Muscle, bone, and fat crosstalk: The biological role of myokines, osteokines, and adipokines, Curr. Osteopor. Rep. source

In the paper

“This environment constitutes fertile soil for atherosclerosis’s chronic inflammatory process, a prelude to several cardiovascular conditions [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

“Angptl8 is a hepatokine related to the reset of diurnal rhythms of hepatic clock, and metabolic genes in mice [88,90,91].”

What the sources say

• Not checked yetcites [88] Potthoff, 2021, Hepatokines and metabolism: Deciphering communication from the liver, Mol. Metab. source
• Not checked yetcites [90] Li, S., Li, J., Pan, R., Cheng, J., Cui, Q., Chen, J., and Yuan, Z. (2021). Sodium rutin extends lifespan and health span in mice including positive impacts on liver health. Br. J. Pharmacol. source
• Not checked yetcites [91] Hou, 2020, The ANGPTL8 rs2278426 (C/T) polymorphism is associated with prediabetes and type 2 diabetes in a han Chinese population in Hebei province, Int. J. Endocrinol. source

In the paper

“Far beyond understanding each adipokine, myokine, or hepatokine’s actions alone, it is important to underline that these cytokines act together in the body, forming 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 DM2, obesity, metabolic syndrome, and CVD”

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

“For these reasons, physical exercise is a powerful ally in the prevention and improvement of the prognosis of cardiovascular diseases, DM2, and obesity, since it influences the predominance of the secretion of anti-inflammatory myokines, adipokines, and hepatokines, such as irisin, IL-6, IL -15, myonectin, adiponectin, FGF21 (which mitigate the harmful effects of myostatin), TNF-α, resistin, cheme”

What the sources say

• Not checked yetcites [101] Chen, 2020, Myokines mediate the cross talk between skeletal muscle and other organs, J. Cell. Physiol. source

In the paper

“Therefore, the assessment of circulating adipokines may be relevant in the analysis of cardiometabolic risk [110].”

What the sources say

• Not checked yetcites [110] Ouerghi, 2020, Association of selected adipokines with metabolic syndrome and cardio-metabolic risk factors in young males, Cytokine source

In the paper

“It is also negatively related to the pathological changes in NAFLD, suggesting that the lower adropin expression may play an important role in the progression of NAFLD to severe NASH.”

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

“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

“The main hepatokines related to insulin resistance, a fundamental factor in the development of DM2 and obesity, are fetuin-A, hepassocin, LECT2, and selenoprotein.”

What the sources say

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

In the paper

“Substances that act as adipokines, myokines, and hepatokines, such as FGF21, are essential for controlling glucose and lipid metabolism.”

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

“Elevated levels of leptin and chemerin, for example, may be negatively associated with cardiometabolic health, just as adiponectin and omentin-1 may be positively associated.”

What the sources say

• Not checked yetcites [110] Ouerghi, 2020, Association of selected adipokines with metabolic syndrome and cardio-metabolic risk factors in young males, Cytokine source

In the paper

“Subsequently, the hepatokine most positively associated with CVD is adropin.”

In the paper

“As such, it is an important therapeutic target of protection against muscle and liver insulin resistance induced by lipids and DM2 [106,107].”

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

“It is also negatively related to the pathological changes in NAFLD, suggesting that the lower adropin expression may play an important role in the progression of NAFLD to severe NASH.”

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

“It has also been identified that follistatin directly protects β cells when induced by exercise, together with irisin [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

“Elevated levels of leptin and chemerin, for example, may be negatively associated with cardiometabolic health, just as adiponectin and omentin-1 may be positively associated.”

What the sources say

• Not checked yetcites [110] Ouerghi, 2020, Association of selected adipokines with metabolic syndrome and cardio-metabolic risk factors in young males, Cytokine 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

“In addition to insulin resistance, fetuin-A can also promote lipotoxicity in β cells through the TLR4-JNK-NF-kB signaling pathway [65].”

What the sources say

• Not checked yetcites [65] Shen, 2015, Fetuin A promotes lipotoxicity in β cells through the TLR4 signaling pathway and the role of pioglitazone in anti-lipotoxicity, Mol. Cell. Endocrinol. source