How Exercise Affects Exerkines in Metabolic Syndrome

Abstract

Metabolic syndrome is a complex condition characterized by central obesity, hyperglycemia, insulin resistance, inflammation, dyslipidemia and hypertension which predispose individuals toward diabetes and cardiovascular disorder. The aim of this review is to investigate some selected novel adipokines, myokines, and hepatokines whose secretion is affected by exercise and improves metabolic syndrome. According to epidemiological studies, the incidence of metabolic syndrome is expected to increase every year, which predisposes health organizations with big challenges. Regular exercise stands as a preventive tool for metabolic syndrome, not only by improving blood circulation, but also through alterations in exerkines. The proteins are secreted by adipose tissue (adipokines), skeletal muscles (myokines), liver (hepatokines) or other tissues during exercise. Interestingly, adipo-myo-hepatokines are categorized into inflammatory and anti-inflammatory peptides, and exercise either reduces or elevates them. The beneficial effects of exercise for various physiological systems, and more importantly prevention and treatment of metabolic syndrome, still have remained mysterious. According to the literature, some of the anti-inflammatory exerkines cooperate in the metabolic homeostasis of organisms by increasing blood flow, muscle mass, and glucose utilization and improving insulin sensitivity and fatty acid oxidation.

Keywords

metabolic syndrome - exerkines - physical activity - adipokines - myokines - hepatokines

Publication History

Received: 08 May 2025

Accepted after revision: 09 October 2025

Article published online:
10 November 2025

• References

• 1 Martemucci G, Fracchiolla G, Muraglia M. et al. A narrative review from the oxidative stress to the management of related diseases. Antioxidants 2023; 12: 2091
• 2 Lehr S, Hartwig S, Sell H.. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. PROTEOMICS–Clinical Applications. 2012; 6: 91-101
• 3 Tanianskii DA, Jarzebska N, Birkenfeld AL.. Beta-aminoisobutyric acid as a novel regulator of carbohydrate and lipid metabolism. Nutrients 2019; 11: 524
• 4 Barbalho SM, Neto EV, De Alvares Goulart R. et al. Myokines: a descriptive review. J Sports Med Phys Fit 2020; 60: 1583-1589
• 5 Leal LG, Lopes MA, Batista ML. Physical exercise-induced myokines and muscle-adipose tissue crosstalk: a review of current knowledge and the implications for health and metabolic diseases. Front Physiol 2018; 9: 1307
• 6 Fu CP, Oczypok EE, Ali H. et al. Effect of physical activity in a weight loss program on circulating total ANGPTL8 concentrations in northern Americans with obesity: A prospective randomized controlled trial. Nutrition, Metab Cardiovascular Dis 2022; 32: 1725-1733
• 7 Yang Y, Beigneux AP, Song W. et al. Hypertriglyceridemia in Apoa5–/–mice results from reduced amounts of lipoprotein lipase in the capillary lumen. J Clin Invest 2023; 133: e172600
• 8 Hoffmann WG, Chen YQ, Schwartz CS. et al. Effects of exercise training on ANGPTL3/8 and ANGPTL4/8 and their associations with cardiometabolic traits. J Lipid Res 2024; 65: 100495
• 9 Gray NE, Lam LN, Yang K. et al. Angiopoietin-like 4 (Angptl4) protein is a physiological mediator of intracellular lipolysis in murine adipocytes. J Biol Chem 2012; 287: 8444-8456
• 10 Hoffmann C, Weigert C.. Skeletal muscle as an endocrine organ: the role of myokines in exercise adaptations. Cold Spring Harb Perspect Med 2017; 7: a029793
• 11 Liu X, Dhananjayan R, Wang X. et al. Differential regulation of ANGPTL4 by endurance and resistance exercise training in obese humans. JCI Insight 2024; 9: 177284
• 12 Kersten S.. Regulation of lipid metabolism via angiopoietin-like proteins. J Nutr Biochem 2021; 94: 108631
• 13 Wang Y, McNutt MC, Banfi S. et al. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis. Proc Natl Acad Sci 2015; 112: 11630-11635
• 14 Ginsberg HN, Goldberg IJ.. Broadening the scope of dyslipidemia therapy by targeting APOC3 (apolipoprotein C3) and ANGPTL3 (angiopoietin-like protein 3). Arterioscler, Thromb, Vasc Biol 2023; 43: 388-398
• 15 Sylvers-Davie KL, Markan KR, Pearson MJ. et al. ANGPTL4 links metabolic and inflammatory control of glucose and lipid metabolism. Am J Physiol Endocrinol Metab 2021; 320: E140-E154
• 16 Zhang R, Zhang K.. An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues. Prog Lipid Res 2022; 85: 101140
• 17 Chen YQ, Pottanat TG, Siegel RW. et al. Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids [S]. J Lipid Res 2020; 61: 1203-1220
• 18 Ingerslev B, Hansen JS, Hoffmann C. et al. ANGPTL4 is increased after acute exercise and influences glucose uptake in human skeletal muscle. J Clin Endocrinol Metab 2017; 102: 3723-3732
• 19 Bourebaba L, Marycz K.. Pathophysiological implication of fetuin-A glycoprotein in the development of metabolic disorders: a concise review. J Clin Med 2019; 8: 2033
• 20 Winn NC, Liu Y, Rector RS. et al. Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity—a randomized trial. Metabolism 2018; 78: 128-40.
• 21 Stefan N, Kantartzis K, Haring H-U.. Causes and metabolic consequences of fatty liver. Endocr Rev 2008; 29: 939-960
• 22 Trepanowski J, Mey J, Varady K.. Fetuin-A: a novel link between obesity and related complications. Int J Obes 2015; 39: 734-741
• 23 Malin SK, Del Rincon JP, Huang H. et al. Exercise-induced lowering of fetuin-A may increase hepatic insulin sensitivity. Med Sci Sports Exerc 2014; 46: 2085
• 24 Nazari M, Kordi MR, Minasian V. et al. Ameliorating effect of 6-week swimming exercise on mice with experimental autoimmune encephalomyelitis (EAE) by reducing fetuin-A and increasing AMPK & NAD⁺ levels in liver tissue. Iran J Basic Med Sci 2022; 25: 1016
• 25 Zhang L-Y, Liu T, Teng Y-Q. et al. Effect of a 12-week aerobic exercise training on serum fetuin-A and adipocytokine levels in type 2 diabetes. Exp Clin Endocrinol Diabetes 2018; 126: 487-492
• 26 Ramírez-Vélez R, García-Hermoso A, Hackney AC. et al. Effects of exercise training on Fetuin-a in obese, type 2 diabetes and cardiovascular disease in adults and elderly: a systematic review and Meta-analysis. Lipids Health Dis 2019; 18: 1-11
• 27 Chattopadhyay M, Mukherjee S, Chatterjee SK. et al. Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte is regulated by Fetuin A. Cell Signal 2018; 42: 67-76
• 28 Lee S, Norheim F, Gulseth HL. et al. Interaction between plasma fetuin-A and free fatty acids predicts changes in insulin sensitivity in response to long-term exercise. Physiol Rep 2017; 5: e13183
• 29 Pasmans K, Goossens GH, Groenhuijzen E. et al. Fetuin B in white adipose tissue induces inflammation and is associated with peripheral insulin resistance in mice and humans. Obesity 2024; 32: 517-27.
• 30 Wang D, Liu Y, Liu S. et al. Serum fetuin-B is positively associated with intrahepatic triglyceride content and increases the risk of insulin resistance in obese Chinese adults: A cross-sectional study. J Diabetes 2018; 10: 581-588
• 31 Olivier E, Soury E, Ruminy P. et al. Fetuin-B, a second member of the fetuin family in mammals. Biochem J 2000; 350: 589-597
• 32 Peter A, Kovarova M, Staiger H. et al. The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans. Am J Physiol Endocrinol Metab 2018; 314: E266-E273
• 33 Xue S, Han H, Rui S. et al. Serum Fetuin-B Levels Are Elevated in Women with Metabolic Syndrome and Associated with Increased Oxidative Stress. Oxid Med Cell Longev 2021; 2021: 6657658
• 34 Gorbanian B, Saberi Y.. Changes in Fetuin-B and RBP4 During A Course of High-Intensity Interval Training in Women with Nonalcoholic Fatty Liver. J Babol Univ Med Sci 2021; 23: 398
• 35 Keihanian A, Arazi H, Kargarfard M.. Effects of aerobic versus resistance training on serum fetuin-A, fetuin-B, and fibroblast growth factor-21 levels in male diabetic patients. Physiol Int 2019; 106: 70-80
• 36 Zhang S, Zhou Y, Lin Y. et al. Effects of combined aerobic and resistance training on Fetuin-B levels in metabolic syndrome: A controlled clinical trial. J Clin Endocrinol Metab 2023; 108: 985-994
• 37 Li H, Zhu D, Zeng Y. et al. Comparison of aerobic and resistance training on hepatic fetuin-B in overweight adults. Metabolism 2022; 133: 155234
• 38 Huang C, Wang Y, Zhang X. et al. Fetuin-B suppresses mitochondrial biogenesis and fatty acid oxidation through AMPK inhibition. Am J Physiol Endocrinol Metab 2023; 324: E13-E22
• 39 Ke F, Xue G, Jiang X. et al. Combination of asprosin and adiponectin as a novel marker for diagnosing non-alcoholic fatty liver disease. Cytokine 2020; 134: 155184
• 40 Zhang Z, Zhu L, Wang Z. et al. Can the new adipokine asprosin be a metabolic troublemaker for cardiovascular diseases? A state-of-the-art review. Prog Lipid Res 2023; 91: 101240
• 41 Zhong L, Long Y, Wang S. et al. Continuous elevation of plasma asprosin in pregnant women complicated with gestational diabetes mellitus: A nested case-control study. Placenta 2020; 93: 17-22
• 42 Hosseini ZS, Heydari-Zarnagh H, Behmanesh M. et al. Maternal exposure to air pollution and umbilical asprosin concentration, a novel insulin-resistant marker. Chemosphere 2021; 268: 129228
• 43 Barteková M, Adameová A, Görbe A. et al. Natural and synthetic antioxidants targeting cardiac oxidative stress and redox signaling in cardiometabolic diseases. Free Radic Biol Med 2021; 169: 446-77.
• 44 Rahim HA, Damirchi A, Babaei P.. Comparison of HIIT and MICT and further detraining on metabolic syndrome and asprosin signaling pathway in metabolic syndrome model of rats. Sci Rep 2024; 14: 11313
• 45 Wang Y, Qu H, Wang W. et al. Effects of different exercise modalities on circulating Asprosin: A randomized controlled trial. Metabolism 2023; 139: 155403
• 46 Schiffer L, Barnard L, Baranowski ES. et al. Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review. J Steroid Biochem Mol Biol 2019; 194: 105439
• 47 Maylem ERS, Spicer LJ, Atabay EP. et al. A potential role of fibrillin-1 (FBN1) mRNA and asprosin in follicular development in water buffalo. Theriogenology 2022; 178: 67-72
• 48 Alamri HS, Bahammam SA, Aldhubayel AM. et al. The emerging role of asprosin in obesity and metabolic disorders: A critical review. Front Endocrinol (Lausanne) 2024; 15: 1243769
• 49 Ridker PM, Rifai N, Clearfield M. et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959-1965
• 50 Broch M, Gómez JM, Auguet MT. et al. Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. Obes Surg 2010; 20: 1258-1264
• 51 Taghian F.. Concurrent exercise and aerobic-resistance exercise ameliorate the serum of Retinol-Binding Protein-4 level and insulin resistance in postmenopausal women. Sci Sports 2022; 37: 736-744
• 52 Choi K, Kim T, Yoo H. et al. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol 2009; 70: 569-574
• 53 DeBoer MD.. Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition 2013; 29: 379-386
• 54 Flores-Cortez YA, Barragán-Bonilla MI, Mendoza-Bello JM. et al. Interplay of retinol binding protein 4 with obesity and associated chronic alterations. Mol Med Rep 2022; 26: 1-12
• 55 Xia Y, Wang Y, Jin L. et al. Combined training reduces RBP4 and improves insulin sensitivity in obese adults: A randomized trial. Diabetes Metab Res Rev 2023; 39: e3611
• 56 Rodríguez-Gutiérrez R, Marroquín JL, Tamez-Velarde M. et al. Resistance training does not alter circulating RBP4 in elderly adults with metabolic syndrome. Aging Clin Exp Res 2022; 34: 1933-1940
• 57 Wang F, Zhao Y, Liu X. et al. Genetic variants in RBP4 gene modulate the metabolic response to exercise in type 2 diabetes. Gene 2023; 873: 147517
• 58 Zheng C, Chen Y, Wu Z.. Aerobic exercise attenuates endothelial RBP4-induced inflammation and oxidative stress via PGC-1α/Nrf2 pathway. Redox Biol 2024; 63: 102748
• 59 Feng M, Jia S.. Dual effect of WISP-1 in diverse pathological processes. Chin J Cancer Res 2016; 28: 553
• 60 Murahovschi V, Pivovarova O, Ilkavets I. et al. WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes 2015; 64: 856-866
• 61 Hörbelt TTC, Markova M, Herzfeld de Wiza D. et al. The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes. Diabetologia 2018; 61: 2054-2065
• 62 Jung TW, Kang K, Goh J. et al. WISP1 promotes non-alcoholic fatty liver disease and skeletal muscle insulin resistance via TLR4/JNK signaling. J Cell Physiol 2018; 233: 6077-6087
• 63 Ahmed SM. et al. WISP1 inhibits insulin signaling via JNK activation in adipose tissue: relevance to obesity-induced IR. Am J Physiol Endocrinol Metab 2023; 325: E213-E221
• 64 Chang JSK, Kong TH, Kong ID.. Exercise intervention lowers aberrant serum WISP-1 levels with insulin resistance in breast cancer survivors: A randomized controlled trial. Sci Rep 2020; 10: 10898
• 65 Tayebi SM, Saeidi A, Shahghasi R. et al. The Eight-Week Circuit Resistance Training Decreased the Serum Levels of WISP-1 and WISP-2 in Individuals with Type 2 Diabetes. Ann Appl Sport Sci 2023; 11: e1290
• 66 Mirr M, Owecki M.. An Update to the WISP-1/CCN4 Role in Obesity, Insulin Resistance and Diabetes. Medicina 2021; 57: 100
• 67 Taniguchi M. et al. Exercise-induced changes in WISP1 depend on inflammation status in older adults. Aging Clin Exp Res 2022; 34: 2249-2256
• 68 Chen C, Wang Y, Liu H. et al. AMPK activation downregulates Wnt/WISP1 signaling in high-fat diet models. Biochem Pharmacol 2024; 212: 115636
• 69 Barlow JP, Karstoft K, Vigelsø A. et al. Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism. Metab Open 2020; 7: 100053
• 70 Roberts Lee D, Boström P, O’Sullivan John F. et al. β-Aminoisobutyric acid induces browning of white fat and hepatic β-Oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab 2014; 19: 96-108
• 71 Stautemas J, Van Kuilenburg AB, Stroomer L. et al. Acute aerobic exercise leads to increased plasma levels of R-and S-β-aminoisobutyric acid in humans. Front Physiol 2019; 10: 1240
• 72 Li D. et al. BAIBA induces thermogenic gene expression through PGC-1α in WAT. Mol Cell Endocrinol 2023; 562: 112932
• 73 Jung TW, Park HS, Choi GH. et al. β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway. J Biomed Sci 2018; 25: 1-9
• 74 Yi X, Yang Y, Li T. et al. Signaling metabolite β-aminoisobutyric acid as a metabolic regulator, biomarker, and potential exercise pill. Front Endocrinol 2023; 14: 1192458
• 75 Wang Y. et al. BAIBA suppresses inflammation in adipose tissue and liver. J Endocrinol Invest 2023; 46: 729-738
• 76 Nishii K, Aizu N, Yamada K.. Review of the health-promoting effects of exercise and the involvement of myokines. Fujita Med J 2023; 9: 171-178
• 77 Arefi Shirvan R, Ghorbanian B, Ghorbanzadeh B.. The effect of twelve weeks of aerobic exercise on the serum levels of angiopoietin-like protein 4 (angptl4) and beta-aminoisobutyric acid (baiba) in men with metabolic syndrome. J Sport Biosci 2022; 14: 19-32
• 78 Gómez-Gómez E. et al. Plasma BAIBA as a predictor of exercise-induced metabolic adaptation. Obes (Silver Spring) 2022; 30: 360-367
• 79 Zhang Y. et al. BAIBA regulates hepatic FGF21 and PPARα expression. J Hepatol 2024; 80: 145-154
• 80 Silva F. et al. BAIBA signaling and its therapeutic potential in metabolic syndrome: Gaps and prospects. Trends Endocrinol Metab 2024; 35: 389-400
• 81 Medicine NLo. TGFB1 transforming growth factor beta 1 [Homo sapiens (human)]. 2024 https://wwwncbinlmnihgov/
• 82 Yadav H, Quijano C, Kamaraju AK. et al. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metab 2011; 14: 67-79
• 83 Santos A. et al. TGF-β1 as a key player in metabolic inflammation. Trends Endocrinol Metab 2022; 33: 679-694
• 84 Liu H, Chen Y-G.. The interplay between TGF-β signaling and cell metabolism. Front Cell Dev Biol 2022; 10: 846723
• 85 Takahashi H, Alves CR, Stanford KI. et al. TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism. Nat Metab 2019; 1: 291-303
• 86 Nilchian A, Giotopoulou N, Sun W. et al. Different regulation of Glut1 expression and glucose uptake during the induction and chronic stages of TGFβ1-induced EMT in breast cancer cells. Biomolecules 2020; 10: 1621
• 87 Mehdipoor M, Damirchi A, Babaei P.. Concurrent vitamin D supplementation and exercise training improve cardiac fibrosis via TGF-β/Smad signaling in myocardial infarction model of rats. J Physiol Biochem 2021; 77: 75-84
• 88 Colberg SR, Sigal RJ, Fernhall B. et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 2010; 33: e147-e167
• 89 Verhagen SN, Buijsrogge MP, Vink A. et al. Secretion of adipocytokines by perivascular adipose tissue near stenotic and non-stenotic coronary artery segments in patients undergoing CABG. Atherosclerosis 2014; 233: 242-247
• 90 Di Meo S, Iossa S, Venditti P.. Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training. J Endocrinol 2017; 234: R159-R181
• 91 Ruegsegger GN, Booth FW.. Health benefits of exercise. Cold Spring Harb Perspect Med 2018; 8: a029694
• 92 Ouchi N, Parker JL, Lugus JJ. et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunology 2011; 11: 85-97
• 93 Wong GW, Wang J, Hug C. et al. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci 2004; 101: 10302-10307
• 94 Seldin MM, Tan SY, Wong GW.. Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord 2014; 15: 111-123
• 95 Rodriguez S, Lei X, Petersen PS. et al. Loss of CTRP1 disrupts glucose and lipid homeostasis. Am J Physiol Endocrinol Metab 2016; 311: E678-E697
• 96 Emamgholipour S, Moradi N, Beigy M. et al. The association of circulating levels of complement-C1q TNF-related protein 5 (CTRP5) with nonalcoholic fatty liver disease and type 2 diabetes: a case–control study. Diabetol Metab Syndrome 2015; 7: 1-12
• 97 Schmid A, Kopp A, Aslanidis C. et al. Regulation and function of C1Q/TNF-related protein-5 (CTRP-5) in the context of adipocyte biology. Exp Clin Endocrinol & Diabetes 2013; 121: 310-317
• 98 Peterson JM, Seldin MM, Wei Z. et al. CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism. Am J Physiol Gastrointestinal Liver Physiol 2013; 305: G214-G224
• 99 Wei Z, Lei X, Petersen PS. et al. Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice. Am J Physiol Endocrinol Metab 2014; 306: E779-E790
• 100 Wei Z, Peterson JM, Lei X. et al. C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J Biol Chem 2012; 287: 10301-10315
• 101 Sebin SO, Sebin E, Gencoglu C. et al. Aerobic exercise in cold weather may affect metabolic diseases and bone-cartilage formation by increasing CTRP-3 levels. Eur J Sport Sci 2024; 24: 149-155
• 102 Zarei M, Nakhzari Khodakheir J.. Comparing the Effect of High Intensity Interval Training and Intense Resistance Training on Asprosin and C1q/Tumor Necrosis Factor Related Protein1 Levels in Overweight and Obese Men. Iran J Diabetes Metab 2023; 23: 225-235
• 103 Yamamoto M. et al. Exercise intensity determines CTRP response in obese adults. Obes Res Clin Pract 2022;16. 322-328
• 104 Ouchi N, Walsh K.. Cardiovascular and metabolic regulation by the Adiponectin/C1q/tumor necrosis factor–related protein family of proteins. Am Heart Assoc 2012; 125: 3066-3068
• 105 Little HC, Rodriguez S, Lei X. et al. Myonectin deletion promotes adipose fat storage and reduces liver steatosis. FASEB J 2019; 33: 8666
• 106 Park T-J, Park A, Kim J. et al. Myonectin inhibits adipogenesis in 3T3-L1 preadipocytes by regulating p38 MAPK pathway. BMB Rep 2021; 54: 124
• 107 Seldin MM, Peterson JM, Byerly MS. et al. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012; 287: 11968-11980
• 108 Koohestani Sini Z, Afzalpour ME, Mohammadnia Ahmadi M. et al. The Effect of Aerobic Continuous Training on Myonectin, Insulin Resistance and Liver Enzymes in Rats with Nonalcoholic Fatty Liver Disease. Ann Appl Sport Sci 2020; 8 e-ISSN: 2322–4479; p-ISSN: 2476–4981
• 109 Vatannejad A, Fadaei R, Salimi F. et al. Plasma Complement C1q/tumor necrosis factor-related protein 15 concentration is associated with polycystic ovary syndrome. PLoS One 2022; 17: e0263658
• 110 Fang H. et al. CTRP15 regulates hepatic insulin signaling via PI3K/Akt/FoxO1. Diabetes 2023; 72: 1045-1056
• 111 Kim Y. et al. PPARα signaling mediates CTRP15-induced FA oxidation. Mol Metab 2024; 82: 101684
• 112 Pourranjbar M, Arabnejad N, Naderipour K. et al. Effects of aerobic exercises on serum levels of myonectin and insulin resistance in obese and overweight women. J Med Life 2018; 11: 381
• 113 Brenmoehl J, Albrecht E, Komolka K. et al. Langhammer M, Hoeflich A, et al. Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise. Int J Biol Sci 2014; 10: 338
• 114 Liu Z. et al. Clinical translation of CTRP-based therapies: current status. J Transl Endocrinol 2024; 2: e39-e49
• 115 Kleinert M, Clemmensen C, Sjøberg KA. et al. Exercise increases circulating GDF15 in humans. Mol Metab 2018; 9: 187-191
• 116 Emmerson PJ, Wang F, Du Y. et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat Med 2017; 23: 1215-1219
• 117 Aguilar-Recarte D, Barroso E, Palomer X. et al. Knocking on GDF15’s door for the treatment of type 2 diabetes mellitus. Trends Endocrinol Metab 2022; 33: 741-754
• 118 Lockhart SM. et al. The GDF15-GFRAL axis in energy balance. Endocr Rev 2023; 44: 16-45
• 119 Plomgaard P, Hansen JS, Townsend LK. et al. GDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans. Front Endocrinol 2022; 13: 1037948
• 120 Zhang M, Sun W, Qian J. et al. Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid β-oxidation and ketogenesis via activating XBP1 signaling in liver. Redox Biol 2018; 16: 87-96
• 121 Mehta R. et al. Exercise-induced GDF15 and adipose tissue metabolism. J Physiol 2022; 600: 395-408
• 122 Deng Y. et al. Differential GDF15 response to training intensity. Metabolism 2023; 139: 155363
• 123 Dostalova I. et al. GDF15 as a marker of exercise-induced metabolic stress. Eur J Clin Invest 2024; 54: e14032
• 124 Staiger H, Keuper M, Berti L. et al. Fibroblast growth factor 21—metabolic role in mice and men. Endocr Rev 2017; 38: 468-488
• 125 Huang Z, Xu A, Cheung BM.. The potential role of fibroblast growth factor 21 in lipid metabolism and hypertension. Curr Hypertens Rep 2017; 19: 1-6
• 126 Liang Q, Zhong L, Zhang J. et al. FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting. Diabetes 2014; 63: 4064-4075
• 127 Kim H-j SongW.. Resistance training increases fibroblast growth factor-21 and irisin levels in the skeletal muscle of Zucker diabetic fatty rats. J Exerc Nutr Biochem 2017; 21: 50
• 128 Charoenphandhu N, Suntornsaratoon P, Krishnamra N. et al. Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats. J Bone Miner Metab 2017; 35: 142-149
• 129 Geng L, Liao B, Jin L. et al. Exercise alleviates obesity-induced metabolic dysfunction via enhancing FGF21 sensitivity in adipose tissues. Cell Rep 2019; 26: 2738-52.e4
• 130 Kaufman A, Abuqayyas L, Denney WS. et al. AKR-001, an Fc-FGF21 analog, showed sustained pharmacodynamic effects on insulin sensitivity and lipid metabolism in type 2 diabetes patients. Cell Rep Med 2020; 1: 100057
• 131 Tanimura Y, Aoi W, Takanami Y. et al. Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation. Physiol Rep 2016; 4: e12828
• 132 Vecchiatto B, de Castro TL, Muller CR. et al. Physical exercise-induced FGF-21 to fight obesity: An update review. Obesities 2022; 2: 372-379 Hansen JS, Pedersen BK, Xu G, et al. Exercise-induced secretion of FGF21 and follistatin are blocked by pancreatic clamp and impaired in type 2 diabetes. J Clin Endocrinol Metab 2016; 101: 2816–2825.
• 133 Kim KH, Kim SH, Min YK. et al. Exercise-induced FGF21 expression is mediated by the PGC-1α–AMPK–SIRT1 axis in skeletal muscle. J Endocrinol 2013; 217: 203-210 Loyd C, Magrisso IJ, Haas M, et al. Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding. J Appl Physiol 2016; 121: 687–698.
• 134 Alizadeh H.. Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator. Cytokine 2022; 157: 155952
• 135 Jamal MH, Abu-Farha M, Al-Khaledi G. et al. Effect of sleeve gastrectomy on the expression of meteorin-like (METRNL) and Irisin (FNDC5) in muscle and brown adipose tissue and its impact on uncoupling proteins in diet-induced obesity rats. Surg Obes Relat Dis 2020; 16: 1910-1918
• 136 Zheng S-l, Li Z-y, Song J. et al. Metrnl: a secreted protein with new emerging functions. Acta Pharmacol Sin 2016; 37: 571-579
• 137 Rao RR, Long JZ, White JP. et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 2014; 157: 1279-1291
• 138 Jung CH, Kim BY, Mok JO.. Subfatin (Meteorin-like): A new player in skeletal muscle and adipose tissue. Front Physiol 2018; 9: 1906
• 139 Eaton M, Granata C, Barry J. et al. Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle. J Sport Health Sci 2018; 7: 191-196
• 140 Lee DE, McKay LK, Bareja A. et al. Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling. Nat Commun 2022; 13: 7613
• 141 Shabani P, Vahdatpour B, Sadeghi A.. The role of Metrnl in metabolic regulation, tissue repair, and exercise adaptation. J Physiol Biochem 2023; 79: 231-241
• 142 Aydin S, Kuloglu T.. Metrnl as a novel adipomyokine in exercise and metabolic health: Current knowledge and future directions. Clin Chim Acta 2022; 527: 104-112
• 143 Crisol BM, Veiga CB, Lenhare L. et al. Nicotinamide riboside induces a thermogenic response in lean mice. Life Sci 2018; 211: 1-7
• 144 Macêdo APA, Muñoz VR, Cintra DE. et al. 12, 13-diHOME as a new therapeutic target for metabolic diseases. Life Sci 2022; 290: 120229
• 145 Vasan SK, Noordam R, Gowri MS. et al. The proposed systemic thermogenic metabolites succinate and 12, 13-diHOME are inversely associated with adiposity and related metabolic traits: evidence from a large human cross-sectional study. Diabetologia 2019; 62: 2079-2087
• 146 Pinckard KM, Shettigar VK, Wright KR. et al. A novel endocrine role for the BAT-released lipokine 12, 13-diHOME to mediate cardiac function. Circulation 2021; 143: 145-159
• 147 Gurup A, Yakal S, Tarçın G. et al. Effect of acute exercise on 12, 13-dihydroxy-9Z-octadecenoic acid (12, 13-diHOME) levels in obese male adolescents. Clin Endocrinol 2023; 99: 174-181
• 148 Gad SA, Smith H, Roberts LD.. Metabolic Small Talk During Exercise: The Role of Metabokines and Lipokines in Interorgan Signalling. Curr OpEndocr Metab Res 2024; 35: 100525
• 149 Nieman DC, Pence BD.. Exercise immunology: Future directions. J Sport Health Sci 2020; 9: 432-445
• 150 Stanford KI, Lynes MD, Takahashi H. et al. 12, 13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell Metab 2018; 27: 1111-20.e3
• 151 Geissler A, Ryzhov S, Sawyer DB.. Neuregulins: protective and reparative growth factors in multiple forms of cardiovascular disease. Clin Sci 2020; 134: 2623-2643
• 152 Tutunchi H, Ostadrahimi A, Hosseinzadeh-Attar MJ. et al. A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances. Obes Rev 2020; 21: e12952
• 153 Fève B, Bastard C, Fellahi S. editors New adipokines. Annales d’endocrinologie. 2016. Elsevier;
• 154 Saeidi A, Shishvan SR, Soltani M. et al. Differential effects of exercise programs on neuregulin 4, body composition and cardiometabolic risk factors in men with obesity. Front Physiol 2022; 12: 797574
• 155 Chen M, Li Y, Zhu JY. et al. Exercise-induced adipokine Nrg4 alleviates MASLD by disrupting hepatic cGAS-STING signaling. Cell Rep 2025; 44: 115251 Epub ahead of print. PMID: 39891907.
• 156 Jabbari N. et al. Exercise training modulates adipokines in metabolic disease: a mechanistic overview. Physiol Res 2022; 71 (Suppl. 02) S301-S312
• 157 Gavaldà-Navarro A, Villarroya J, Cereijo R. et al. The endocrine role of brown adipose tissue: An update on actors and actions. Rev Endocr Metab Disord 2022; 23: 1-11
• 158 Heidari J. et al. Effect of different training modalities on Nrg4 and metabolic parameters in overweight subjects. J Diabetes Metab Disord 2021; 20: 785-792
• 159 Oh K-J, Lee DS, Kim WK. et al. Metabolic adaptation in obesity and type II diabetes: myokines, adipokines and hepatokines. Int J Mol Sci 2016; 18: 8
• 160 Canivell S, Rebuffat S, Ruano EG. et al. Circulating SFRP5 levels are elevated in drug-naive recently diagnosed type 2 diabetic patients as compared with prediabetic subjects and controls. Diabetes/Metab Res Rev 2015; 31: 212-219
• 161 Ouchi N, Higuchi A, Ohashi K. et al. Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science 2010; 329: 454-457
• 162 Abou Ziki MD, Mani A.. The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutr Res 2019; 70: 18-25
• 163 El Asmar Z, Terrand J, Jenty M. et al. Convergent signaling pathways controlled by LRP1 (receptor-related protein 1) cytoplasmic and extracellular domains limit cellular cholesterol accumulation. J Biol Chem 2016; 291: 5116-5127
• 164 Ackers I, Malgor R.. Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases. Diabetes Vasc Dis Res 2018; 15: 3-13
• 165 Gustafson B, Hammarstedt A, Hedjazifar S. et al. Restricted adipogenesis in hypertrophic obesity: the role of WISP2, WNT, and BMP4. Diabetes 2013; 62: 2997-3004
• 166 Weir GC.. Glucolipotoxicity, β-cells, and diabetes: the emperor has no clothes. Diabetes 2020; 69: 273-278
• 167 Shi Z, Xu M, Chen X. et al. The regulatory role of SFRP5/WNT5A axis in allergic rhinitis through inhibiting JNK pathway activation and lowering mucin generation in human nasal epithelial cells. Exp Mol Pathol 2021; 118: 104591
• 168 Fayaz E, Damirchi A, Babaei P. et al. Cinnamon extract combined with high-intensity endurance training alleviates metabolic syndrome via non-canonical WNT signaling. Nutrition 2019; 65: 173-178
• 169 Tan X, Wang X, Chu H. et al. SFRP 5 correlates with obesity and metabolic syndrome and increases after weight loss in children. Clin Endocrinol 2014; 81: 363-369
• 170 Leal ML, Lamas L, Aoki MS. et al. Effect of different resistance-training regimens on the WNT-signaling pathway. Eur J Appl Physiol 2011; 111: 2535-2545
• 171 Karki S, Ngo DT, Farb MG. et al. WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in obese humans. Am J Physiol Heart Circ Physiol 2017; 313: H200-H206
• 172 Mir E, Moazzami M, Bijeh N. et al. Changes in SFRP5, WNT5A, HbA1c, BMI, PBF, and insulin resistance in men with type 2 diabetes after 12 weeks of combined exercise (HIIT and resistance). Int J Diabetes Dev Ctries 2020; 40: 248-254