Metabolic Health—The Role of Adipo-Myokines
Abstract
:1. Introduction
2. Definition and Epidemiological Findings
3. Physical Activity, Cardiorespiratory Fitness, and/or Sedentary Behavior and Its Relation to MHO
4. Myokines, Adipokines, and Adipo-Myokines
5. Body Composition and Its Influence on Metabolic Health
6. Early-Life Programming and the Influence of Different Adipokines, Myokines, and Adipo-Myokines
7. Discussion
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
WHO | World Health Organization |
NCDs | Non-Communicable Diseases |
BMI | Body Mass Index |
MONW | Metabolically Obese, Normal Weight |
MUO | Metabolically Unhealth Obese |
MHO | Metabolically Healthy Obese |
IL | Interleukin |
RR | Risk Ratio |
METs | Metabolic Units |
NHANES | National Health and Nutrition Examination Survey |
CVD | Cardiovascular Disease |
NCEP APT III | National Cholesterol Education Program Adult Treatment Panel III |
FSTL 1 | Follistatin-like 1 |
ANGPTL4 | Angiopoietin-like protein 4 |
MCP-1 | Monocyte Chemoattractant Protein-1 |
Metrnl | Meteorin-like hormone |
GPC-4 | Glypican-4 |
TNF-α | Tumor Necrosis Factor alpha |
A-FABP | Adipocyte Fatty Acid-Binding Protein |
BAT | Brown Adipose Tissue |
WAT | White Adipose Tissue |
UCP1 | Uncoupling protein 1 |
FNDC5 | Fibronectin type III domain-containing protein 5 |
PPAR gamma | Peroxisome proliferator-activated receptor gamma |
PGC-1 alpha | Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha |
TFAM | Mitochondrial Transcription Factor A |
BDNF | Brain-Derived Neurotrophic Factor |
SDS | Standard Deviation Scores |
TBARS | Thiobarbituric Acid-Reactive Substances |
Jak | Janus kinase |
STAT | Signal Transducer and Activator of Transcription |
FFA | Free Fatty Acid |
MuRF1 | muscle RING finger 1 |
MAFbx | muscle atrophy F-box |
AMPK | 5′ AMP-activated protein kinase |
References
- The Lancet Public, H. Tackling obesity seriously: The time has come. Lancet Public Health 2018, 3, e153. [Google Scholar] [CrossRef]
- Collaboration, N.C.D.R.F. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 2017, 390, 2627–2642. [Google Scholar] [CrossRef] [Green Version]
- Global, B.M.I.M.C.; Di Angelantonio, E.; Bhupathiraju Sh, N.; Wormser, D.; Gao, P.; Kaptoge, S.; Berrington de Gonzalez, A.; Cairns, B.J.; Huxley, R.; Jackson, C.H.L.; et al. Body-mass index and all-cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 2016, 388, 776–786. [Google Scholar] [CrossRef] [Green Version]
- World Health Organization. Obesity and Overweight. Available online: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (accessed on 6 December 2019).
- Goossens, G.H. The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function. Obes. Facts 2017, 10, 207–215. [Google Scholar] [CrossRef]
- Organisation, W.H. Noncommunicable Diseases. Available online: https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseases (accessed on 6 November 2019).
- Collaborators, G.B.D.R.F. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016, 388, 1659–1724. [Google Scholar] [CrossRef] [Green Version]
- Kralisch, S.; Bluher, M.; Paschke, R.; Stumvoll, M.; Fasshauer, M. Adipokines and adipocyte targets in the future management of obesity and the metabolic syndrome. Mini Rev. Med. Chem. 2007, 7, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Mottola, M.F.; Artal, R. Fetal and maternal metabolic responses to exercise during pregnancy. Early Hum. Dev. 2016, 94, 33–41. [Google Scholar] [CrossRef] [PubMed]
- Steell, L.; Ho, F.K.; Sillars, A.; Petermann-Rocha, F.; Li, H.; Lyall, D.M.; Iliodromiti, S.; Welsh, P.; Anderson, J.; MacKay, D.F.; et al. Dose-response associations of cardiorespiratory fitness with all-cause mortality and incidence and mortality of cancer and cardiovascular and respiratory diseases: The UK Biobank cohort study. Br. J. Sports Med. 2019, 53, 1371–1378. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Handschin, C.; Spiegelman, B.M. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 2008, 454, 463–469. [Google Scholar] [CrossRef] [Green Version]
- Pedersen, B.K.; Akerstrom, T.C.; Nielsen, A.R.; Fischer, C.P. Role of myokines in exercise and metabolism. J. Appl. Physiol. 2007, 103, 1093–1098. [Google Scholar] [CrossRef] [Green Version]
- Rodriguez, A.; Becerril, S.; Ezquerro, S.; Mendez-Gimenez, L.; Fruhbeck, G. Crosstalk between adipokines and myokines in fat browning. Acta Physiol. (Oxf.) 2017, 219, 362–381. [Google Scholar] [CrossRef]
- Raschke, S.; Eckel, J. Adipo-myokines: Two sides of the same coin--mediators of inflammation and mediators of exercise. Mediat. Inflamm. 2013, 2013, 320724. [Google Scholar] [CrossRef]
- Barker, D.J. Fetal origins of coronary heart disease. BMJ 1995, 311, 171–174. [Google Scholar] [CrossRef]
- Godfrey, K.M.; Barker, D.J. Fetal programming and adult health. Public Health Nutr. 2001, 4, 611–624. [Google Scholar] [CrossRef]
- Ruderman, N.B.; Schneider, S.H.; Berchtold, P. The “metabolically-obese,” normal-weight individual. Am. J. Clin. Nutr. 1981, 34, 1617–1621. [Google Scholar] [CrossRef]
- Sims, E.A. Are there persons who are obese, but metabolically healthy? Metab. Clin. Exp. 2001, 50, 1499–1504. [Google Scholar] [CrossRef]
- Bosello, O.; Donataccio, M.P.; Cuzzolaro, M. Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord. 2016, 21, 165–174. [Google Scholar] [CrossRef]
- Smith, G.I.; Mittendorfer, B.; Klein, S. Metabolically healthy obesity: Facts and fantasies. J. Clin. Investig. 2019, 129, 3978–3989. [Google Scholar] [CrossRef] [Green Version]
- Velho, S.; Paccaud, F.; Waeber, G.; Vollenweider, P.; Marques-Vidal, P. Metabolically healthy obesity: Different prevalences using different criteria. Eur. J. Clin. Nutr. 2010, 64, 1043–1051. [Google Scholar] [CrossRef]
- Iacobini, C.; Pugliese, G.; Blasetti Fantauzzi, C.; Federici, M.; Menini, S. Metabolically healthy versus metabolically unhealthy obesity. Metab. Clin. Exp. 2019, 92, 51–60. [Google Scholar] [CrossRef]
- Kramer, C.K.; Zinman, B.; Retnakaran, R. Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann. Intern. Med. 2013, 159, 758–769. [Google Scholar] [CrossRef] [PubMed]
- Stefan, N.; Haring, H.U.; Hu, F.B.; Schulze, M.B. Metabolically healthy obesity: Epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol. 2013, 1, 152–162. [Google Scholar] [CrossRef]
- Caspersen, C.J.; Powell, K.E.; Christenson, G.M. Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research. Public Health Rep. 1985, 100, 126–131. [Google Scholar] [PubMed]
- Gibbs, B.B.; Hergenroeder, A.L.; Katzmarzyk, P.T.; Lee, I.M.; Jakicic, J.M. Definition, measurement, and health risks associated with sedentary behavior. Med. Sci. Sports Exerc. 2015, 47, 1295–1300. [Google Scholar] [CrossRef] [Green Version]
- Pfeifer, K.; Rutten, A. [National Recommendations for Physical Activity and Physical Activity Promotion]. Gesundheitswesen 2017, 79, S2–S3. [Google Scholar] [CrossRef] [Green Version]
- Myers, J.; Prakash, M.; Froelicher, V.; Do, D.; Partington, S.; Atwood, J.E. Exercise capacity and mortality among men referred for exercise testing. N. Engl. J. Med. 2002, 346, 793–801. [Google Scholar] [CrossRef]
- Myers, J.; McAuley, P.; Lavie, C.J.; Despres, J.P.; Arena, R.; Kokkinos, P. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: Their independent and interwoven importance to health status. Prog. Cardiovasc. Dis. 2015, 57, 306–314. [Google Scholar] [CrossRef]
- Kennedy, A.B.; Lavie, C.J.; Blair, S.N. Fitness or Fatness: Which Is More Important? JAMA 2018, 319, 231–232. [Google Scholar] [CrossRef]
- De Rooij, B.H.; van der Berg, J.D.; van der Kallen, C.J.; Schram, M.T.; Savelberg, H.H.; Schaper, N.C.; Dagnelie, P.C.; Henry, R.M.; Kroon, A.A.; Stehouwer, C.D.; et al. Physical Activity and Sedentary Behavior in Metabolically Healthy versus Unhealthy Obese and Non-Obese Individuals—The Maastricht Study. PLoS ONE 2016, 11, e0154358. [Google Scholar] [CrossRef]
- Camhi, S.M.; Waring, M.E.; Sisson, S.B.; Hayman, L.L.; Must, A. Physical activity and screen time in metabolically healthy obese phenotypes in adolescents and adults. J. Obes. 2013, 2013, 984613. [Google Scholar] [CrossRef]
- Ortega, F.B.; Cadenas-Sanchez, C.; Migueles, J.H.; Labayen, I.; Ruiz, J.R.; Sui, X.; Blair, S.N.; Martinez-Vizcaino, V.; Lavie, C.J. Role of Physical Activity and Fitness in the Characterization and Prognosis of the Metabolically Healthy Obesity Phenotype: A Systematic Review and Meta-analysis. Prog. Cardiovasc. Dis. 2018, 61, 190–205. [Google Scholar] [CrossRef]
- Ortega, F.B.; Lee, D.C.; Katzmarzyk, P.T.; Ruiz, J.R.; Sui, X.; Church, T.S.; Blair, S.N. The intriguing metabolically healthy but obese phenotype: Cardiovascular prognosis and role of fitness. Eur. Heart J. 2013, 34, 389–397. [Google Scholar] [CrossRef]
- Piglowska, M.; Kostka, T.; Drygas, W.; Jegier, A.; Leszczynska, J.; Bill-Bielecka, M.; Kwasniewska, M. Body composition, nutritional status, and endothelial function in physically active men without metabolic syndrome—A 25 year cohort study. Lipids Health Dis. 2016, 15, 84. [Google Scholar] [CrossRef] [Green Version]
- Martinez-Gomez, D.; Ortega, F.B.; Hamer, M.; Lopez-Garcia, E.; Struijk, E.; Sadarangani, K.P.; Lavie, C.J.; Rodriguez-Artalejo, F. Physical Activity and Risk of Metabolic Phenotypes of Obesity: A Prospective Taiwanese Cohort Study in More Than 200,000 Adults. Mayo Clin. Proc. 2019. [Google Scholar] [CrossRef]
- Gorgens, S.W.; Eckardt, K.; Jensen, J.; Drevon, C.A.; Eckel, J. Exercise and Regulation of Adipokine and Myokine Production. Prog. Mol. Biol. Transl. Sci. 2015, 135, 313–336. [Google Scholar] [CrossRef]
- AlKhairi, I.; Cherian, P.; Abu-Farha, M.; Madhoun, A.A.; Nizam, R.; Melhem, M.; Jamal, M.; Al-Sabah, S.; Ali, H.; Tuomilehto, J.; et al. Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin. Cells 2019, 8, 1283. [Google Scholar] [CrossRef] [Green Version]
- Abdolmaleki, F.; Heidarianpour, A. The response of serum Glypican-4 levels and its potential regulatory mechanism to endurance training and chamomile flowers’ hydroethanolic extract in streptozotocin-nicotinamide-induced diabetic rats. Acta Diabetol. 2018, 55, 935–942. [Google Scholar] [CrossRef]
- Bostrom, P.; Wu, J.; Jedrychowski, M.P.; Korde, A.; Ye, L.; Lo, J.C.; Rasbach, K.A.; Bostrom, E.A.; Choi, J.H.; Long, J.Z.; et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481, 463–468. [Google Scholar] [CrossRef]
- Leal, L.G.; Lopes, M.A.; Batista, M.L., Jr. 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. [Google Scholar] [CrossRef]
- Pedersen, B.K.; Febbraio, M.A. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 2012, 8, 457–465. [Google Scholar] [CrossRef]
- Mattiotti, A.; Prakash, S.; Barnett, P.; van den Hoff, M.J.B. Follistatin-like 1 in development and human diseases. Cell Mol. Life Sci. 2018, 75, 2339–2354. [Google Scholar] [CrossRef]
- Seldin, M.M.; Peterson, J.M.; Byerly, M.S.; Wei, Z.; Wong, G.W. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J. Biol. Chem. 2012, 287, 11968–11980. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, F.; Li, Y.; Duan, Y.; Hu, C.A.; Tang, Y.; Yin, Y. Myokines and adipokines: Involvement in the crosstalk between skeletal muscle and adipose tissue. Cytokine Growth Factor Rev. 2017, 33, 73–82. [Google Scholar] [CrossRef] [PubMed]
- Chung, H.S.; Choi, K.M. Adipokines and Myokines: A Pivotal Role in Metabolic and Cardiovascular Disorders. Curr. Med. Chem. 2018, 25, 2401–2415. [Google Scholar] [CrossRef] [PubMed]
- Trayhurn, P.; Drevon, C.A.; Eckel, J. Secreted proteins from adipose tissue and skeletal muscle—Adipokines, myokines and adipose/muscle cross-talk. Arch. Physiol. Biochem. 2011, 117, 47–56. [Google Scholar] [CrossRef] [PubMed]
- Broholm, C.; Laye, M.J.; Brandt, C.; Vadalasetty, R.; Pilegaard, H.; Pedersen, B.K.; Scheele, C. LIF is a contraction-induced myokine stimulating human myocyte proliferation. J. Appl. Physiol. 2011, 111, 251–259. [Google Scholar] [CrossRef]
- Yargic, M.P.; Torgutalp, S.; Akin, S.; Babayeva, N.; Torgutalp, M.; Demirel, H.A. Acute long-distance trail running increases serum IL-6, IL-15, and Hsp72 levels. Appl. Physiol. Nutr. Metab. Physiol. Appl. Nutr. Metab. 2019, 44, 627–631. [Google Scholar] [CrossRef]
- Huh, J.Y.; Panagiotou, G.; Mougios, V.; Brinkoetter, M.; Vamvini, M.T.; Schneider, B.E.; Mantzoros, C.S. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metab. Clin. Exp. 2012, 61, 1725–1738. [Google Scholar] [CrossRef] [Green Version]
- Pekkala, S.; Wiklund, P.K.; Hulmi, J.J.; Ahtiainen, J.P.; Horttanainen, M.; Pollanen, E.; Makela, K.A.; Kainulainen, H.; Hakkinen, K.; Nyman, K.; et al. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J. Physiol. 2013, 591, 5393–5400. [Google Scholar] [CrossRef]
- Norheim, F.; Langleite, T.M.; Hjorth, M.; Holen, T.; Kielland, A.; Stadheim, H.K.; Gulseth, H.L.; Birkeland, K.I.; Jensen, J.; Drevon, C.A. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014, 281, 739–749. [Google Scholar] [CrossRef]
- Nielsen, A.R.; Mounier, R.; Plomgaard, P.; Mortensen, O.H.; Penkowa, M.; Speerschneider, T.; Pilegaard, H.; Pedersen, B.K. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J. Physiol. 2007, 584, 305–312. [Google Scholar] [CrossRef] [PubMed]
- Bazgir, B.; Salesi, M.; Koushki, M.; Amirghofran, Z. Effects of Eccentric and Concentric Emphasized Resistance Exercise on IL-15 Serum Levels and Its Relation to Inflammatory Markers in Athletes and Non-Athletes. Asian J. Sports Med. 2015, 6, e27980. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hingorjo, M.R.; Zehra, S.; Saleem, S.; Qureshi, M.A. Serum Interleukin-15 and its relationship with adiposity Indices before and after short-term endurance exercise. Pak. J. Med. Sci. 2018, 34, 1125–1131. [Google Scholar] [CrossRef] [PubMed]
- Banitalebi, E.; Kazemi, A.; Faramarzi, M.; Nasiri, S.; Haghighi, M.M. Effects of sprint interval or combined aerobic and resistance training on myokines in overweight women with type 2 diabetes: A randomized controlled trial. Life Sci. 2019, 217, 101–109. [Google Scholar] [CrossRef] [PubMed]
- Stautemas, J.; Van Kuilenburg, A.B.P.; Stroomer, L.; Vaz, F.; Blancquaert, L.; Lefevere, F.B.D.; Everaert, I.; Derave, W. Acute Aerobic Exercise Leads to Increased Plasma Levels of R- and S-beta-Aminoisobutyric Acid in Humans. Front. Physiol. 2019, 10, 1240. [Google Scholar] [CrossRef] [Green Version]
- Roberts, L.D.; Bostrom, P.; O’Sullivan, J.F.; Schinzel, R.T.; Lewis, G.D.; Dejam, A.; Lee, Y.K.; Palma, M.J.; Calhoun, S.; Georgiadi, A.; et al. beta-Aminoisobutyric acid induces browning of white fat and hepatic beta-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 2014, 19, 96–108. [Google Scholar] [CrossRef] [Green Version]
- Saghebjoo, M.; Einaloo, A.; Mogharnasi, M.; Ahmadabadi, F. The response of meteorin-like hormone and interleukin-4 in overweight women during exercise in temperate, warm and cold water. Horm. Mol. Biol. Clin. Investig. 2018, 36. [Google Scholar] [CrossRef]
- Broholm, C.; Mortensen, O.H.; Nielsen, S.; Akerstrom, T.; Zankari, A.; Dahl, B.; Pedersen, B.K. Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle. J. Physiol. 2008, 586, 2195–2201. [Google Scholar] [CrossRef]
- Broholm, C.; Pedersen, B.K. Leukaemia inhibitory factor--an exercise-induced myokine. Exerc. Immunol. Rev. 2010, 16, 77–85. [Google Scholar]
- Hjorth, M.; Pourteymour, S.; Gorgens, S.W.; Langleite, T.M.; Lee, S.; Holen, T.; Gulseth, H.L.; Birkeland, K.I.; Jensen, J.; Drevon, C.A.; et al. Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells. Acta Physiol. (Oxf.) 2016, 217, 45–60. [Google Scholar] [CrossRef]
- Micielska, K.; Gmiat, A.; Zychowska, M.; Kozlowska, M.; Walentukiewicz, A.; Lysak-Radomska, A.; Jaworska, J.; Rodziewicz, E.; Duda-Biernacka, B.; Ziemann, E. The beneficial effects of 15 units of high-intensity circuit training in women is modified by age, baseline insulin resistance and physical capacity. Diabetes Res. Clin. Pract. 2019, 152, 156–165. [Google Scholar] [CrossRef] [PubMed]
- Duggal, N.A.; Pollock, R.D.; Lazarus, N.R.; Harridge, S.; Lord, J.M. Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell 2018, 17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cuevas-Ramos, D.; Almeda-Valdes, P.; Meza-Arana, C.E.; Brito-Cordova, G.; Gomez-Perez, F.J.; Mehta, R.; Oseguera-Moguel, J.; Aguilar-Salinas, C.A. Exercise increases serum fibroblast growth factor 21 (FGF21) levels. PLoS ONE 2012, 7, e38022. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.H.; Kim, S.H.; Min, Y.K.; Yang, H.M.; Lee, J.B.; Lee, M.S. Acute exercise induces FGF21 expression in mice and in healthy humans. PLoS ONE 2013, 8, e63517. [Google Scholar] [CrossRef] [PubMed]
- Nederveen, J.P.; Fortino, S.A.; Baker, J.M.; Snijders, T.; Joanisse, S.; McGlory, C.; McKay, B.R.; Kumbhare, D.; Parise, G. Consistent expression pattern of myogenic regulatory factors in whole muscle and isolated human muscle satellite cells after eccentric contractions in humans. J. Appl. Physiol. 2019. [Google Scholar] [CrossRef] [PubMed]
- Luk, H.Y.; Levitt, D.E.; Boyett, J.C.; Rojas, S.; Flader, S.M.; McFarlin, B.K.; Vingren, J.L. Resistance exercise-induced hormonal response promotes satellite cell proliferation in untrained men but not in women. Am. J. Physiol. Endocrinol. Metab. 2019, 317, E421–E432. [Google Scholar] [CrossRef]
- Lim, S.; Choi, S.H.; Koo, B.K.; Kang, S.M.; Yoon, J.W.; Jang, H.C.; Choi, S.M.; Lee, M.G.; Lee, W.; Shin, H.; et al. Effects of aerobic exercise training on C1q tumor necrosis factor alpha-related protein isoform 5 (myonectin): Association with insulin resistance and mitochondrial DNA density in women. J. Clin. Endocrinol. Metab. 2012, 97, E88–E93. [Google Scholar] [CrossRef] [Green Version]
- Pourranjbar, M.; Arabnejad, N.; Naderipour, K.; Rafie, F. Effects of Aerobic Exercises on Serum Levels of Myonectin and Insulin Resistance in Obese and Overweight Women. J. Med. Life 2018, 11, 381–386. [Google Scholar] [CrossRef]
- De Assis, G.G.; Gasanov, E.V.; de Sousa, M.B.C.; Kozacz, A.; Murawska-Cialowicz, E. Brain derived neutrophic factor, a link of aerobic metabolism to neuroplasticity. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2018, 69. [Google Scholar] [CrossRef]
- Church, D.D.; Hoffman, J.R.; Mangine, G.T.; Jajtner, A.R.; Townsend, J.R.; Beyer, K.S.; Wang, R.; La Monica, M.B.; Fukuda, D.H.; Stout, J.R. Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise. J. Appl. Physiol. 2016, 121, 123–128. [Google Scholar] [CrossRef] [Green Version]
- Yakeu, G.; Butcher, L.; Isa, S.; Webb, R.; Roberts, A.W.; Thomas, A.W.; Backx, K.; James, P.E.; Morris, K. Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: Roles of PPARgamma and Th2 cytokines. Atherosclerosis 2010, 212, 668–673. [Google Scholar] [CrossRef] [PubMed]
- Kon, M.; Ebi, Y.; Nakagaki, K. Effects of acute sprint interval exercise on follistatin-like 1 and apelin secretions. Arch. Physiol. Biochem. 2019. [Google Scholar] [CrossRef] [PubMed]
- Gorgens, S.W.; Raschke, S.; Holven, K.B.; Jensen, J.; Eckardt, K.; Eckel, J. Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells. Arch. Physiol. Biochem. 2013, 119, 75–80. [Google Scholar] [CrossRef] [PubMed]
- Scheler, M.; Irmler, M.; Lehr, S.; Hartwig, S.; Staiger, H.; Al-Hasani, H.; Beckers, J.; de Angelis, M.H.; Haring, H.U.; Weigert, C. Cytokine response of primary human myotubes in an in vitro exercise model. Am. J. Physiol. Cell Physiol. 2013, 305, C877–C886. [Google Scholar] [CrossRef] [PubMed]
- Catoire, M.; Mensink, M.; Kalkhoven, E.; Schrauwen, P.; Kersten, S. Identification of human exercise-induced myokines using secretome analysis. Physiol. Genom. 2014, 46, 256–267. [Google Scholar] [CrossRef]
- Saeidi, A.; Jabbour, G.; Ahmadian, M.; Abbassi-Daloii, A.; Malekian, F.; Hackney, A.C.; Saedmocheshi, S.; Basati, G.; Ben Abderrahman, A.; Zouhal, H. Independent and Combined Effects of Antioxidant Supplementation and Circuit Resistance Training on Selected Adipokines in Postmenopausal Women. Front. Physiol. 2019, 10, 484. [Google Scholar] [CrossRef] [Green Version]
- He, Z.; Tian, Y.; Valenzuela, P.L.; Huang, C.; Zhao, J.; Hong, P.; He, Z.; Yin, S.; Lucia, A. Myokine/Adipokine Response to “Aerobic” Exercise: Is It Just a Matter of Exercise Load? Front. Physiol. 2019, 10, 691. [Google Scholar] [CrossRef]
- Prestes, J.; Shiguemoto, G.; Botero, J.P.; Frollini, A.; Dias, R.; Leite, R.; Pereira, G.; Magosso, R.; Baldissera, V.; Cavaglieri, C.; et al. Effects of resistance training on resistin, leptin, cytokines, and muscle force in elderly post-menopausal women. J. Sports Sci. 2009, 27, 1607–1615. [Google Scholar] [CrossRef]
- Becic, T.; Studenik, C.; Hoffmann, G. Exercise Increases Adiponectin and Reduces Leptin Levels in Prediabetic and Diabetic Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Med. Sci. (Basel) 2018, 6, 97. [Google Scholar] [CrossRef] [Green Version]
- Yu, N.; Ruan, Y.; Gao, X.; Sun, J. Systematic Review and Meta-Analysis of Randomized, Controlled Trials on the Effect of Exercise on Serum Leptin and Adiponectin in Overweight and Obese Individuals. Horm. Metab. Res. 2017, 49, 164–173. [Google Scholar] [CrossRef] [Green Version]
- Fedewa, M.V.; Hathaway, E.D.; Ward-Ritacco, C.L.; Williams, T.D.; Dobbs, W.C. The Effect of Chronic Exercise Training on Leptin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sports Med. 2018, 48, 1437–1450. [Google Scholar] [CrossRef] [PubMed]
- Carvalho, L.P.; Basso-Vanelli, R.P.; Di Thommazo-Luporini, L.; Mendes, R.G.; Oliveira-Junior, M.C.; Vieira, R.P.; Bonjorno-Junior, J.C.; Oliveira, C.R.; Luporini, R.; Borghi-Silva, A. Myostatin and adipokines: The role of the metabolically unhealthy obese phenotype in muscle function and aerobic capacity in young adults. Cytokine 2018, 107, 118–124. [Google Scholar] [CrossRef] [PubMed]
- Poelkens, F.; Eijsvogels, T.M.; Brussee, P.; Verheggen, R.J.; Tack, C.J.; Hopman, M.T. Physical fitness can partly explain the metabolically healthy obese phenotype in women. Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc. 2014, 122, 87–91. [Google Scholar] [CrossRef] [PubMed]
- Wedell-Neergaard, A.S.; Krogh-Madsen, R.; Petersen, G.L.; Hansen, A.M.; Pedersen, B.K.; Lund, R.; Bruunsgaard, H. Cardiorespiratory fitness and the metabolic syndrome: Roles of inflammation and abdominal obesity. PLoS ONE 2018, 13, e0194991. [Google Scholar] [CrossRef]
- Wedell-Neergaard, A.S.; Eriksen, L.; Gronbaek, M.; Pedersen, B.K.; Krogh-Madsen, R.; Tolstrup, J. Low fitness is associated with abdominal adiposity and low-grade inflammation independent of BMI. PLoS ONE 2018, 13, e0190645. [Google Scholar] [CrossRef] [Green Version]
- Lee, T.H.; Jeon, W.S.; Han, K.J.; Lee, S.Y.; Kim, N.H.; Chae, H.B.; Jang, C.M.; Yoo, K.M.; Park, H.J.; Lee, M.K.; et al. Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status. Endocrinol. Metab. (Seoul) 2015, 30, 185–194. [Google Scholar] [CrossRef]
- Wildman, R.P.; Muntner, P.; Reynolds, K.; McGinn, A.P.; Rajpathak, S.; Wylie-Rosett, J.; Sowers, M.R. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: Prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch. Intern. Med. 2008, 168, 1617–1624. [Google Scholar] [CrossRef] [Green Version]
- Arsenault, B.J.; Cote, M.; Cartier, A.; Lemieux, I.; Despres, J.P.; Ross, R.; Earnest, C.P.; Blair, S.N.; Church, T.S. Effect of exercise training on cardiometabolic risk markers among sedentary, but metabolically healthy overweight or obese post-menopausal women with elevated blood pressure. Atherosclerosis 2009, 207, 530–533. [Google Scholar] [CrossRef] [Green Version]
- Gomez-Ambrosi, J.; Catalan, V.; Rodriguez, A.; Andrada, P.; Ramirez, B.; Ibanez, P.; Vila, N.; Romero, S.; Margall, M.A.; Gil, M.J.; et al. Increased cardiometabolic risk factors and inflammation in adipose tissue in obese subjects classified as metabolically healthy. Diabetes Care 2014, 37, 2813–2821. [Google Scholar] [CrossRef] [Green Version]
- Bell, J.A.; Kivimaki, M.; Batty, G.D.; Hamer, M. Metabolically healthy obesity: What is the role of sedentary behaviour? Prev. Med. 2014, 62, 35–37. [Google Scholar] [CrossRef] [Green Version]
- Lee, M.W.; Lee, M.; Oh, K.J. Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs. J. Clin. Med. 2019, 8, 854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martinez Munoz, I.Y.; Camarillo Romero, E.D.S.; Garduno Garcia, J.J. Irisin a Novel Metabolic Biomarker: Present Knowledge and Future Directions. Int. J. Endocrinol. 2018, 2018, 7816806. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pilegaard, H.; Saltin, B.; Neufer, P.D. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J. Physiol. 2003, 546, 851–858. [Google Scholar] [CrossRef] [PubMed]
- Fernandez-Marcos, P.J.; Auwerx, J. Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am. J. Clin. Nutr. 2011, 93, 884S–890S. [Google Scholar] [CrossRef] [Green Version]
- Dinas, P.C.; Lahart, I.M.; Timmons, J.A.; Svensson, P.A.; Koutedakis, Y.; Flouris, A.D.; Metsios, G.S. Effects of physical activity on the link between PGC-1a and FNDC5 in muscle, circulating Iotarisin and UCP1 of white adipocytes in humans: A systematic review. F1000Res 2017, 6, 286. [Google Scholar] [CrossRef]
- Fatouros, I.G. Is irisin the new player in exercise-induced adaptations or not? A 2017 update. Clin. Chem. Lab. Med. 2018, 56, 525–548. [Google Scholar] [CrossRef]
- Granata, C.; Jamnick, N.A.; Bishop, D.J. Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle. Sports Med. 2018, 48, 1809–1828. [Google Scholar] [CrossRef]
- Lecker, S.H.; Zavin, A.; Cao, P.; Arena, R.; Allsup, K.; Daniels, K.M.; Joseph, J.; Schulze, P.C.; Forman, D.E. Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure. Circ. Heart Fail 2012, 5, 812–818. [Google Scholar] [CrossRef] [Green Version]
- Huh, J.Y.; Mougios, V.; Kabasakalis, A.; Fatouros, I.; Siopi, A.; Douroudos, I.I.; Filippaios, A.; Panagiotou, G.; Park, K.H.; Mantzoros, C.S. Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. J. Clin. Endocrinol. Metab. 2014, 99, E2154–E2161. [Google Scholar] [CrossRef] [Green Version]
- Alvehus, M.; Boman, N.; Soderlund, K.; Svensson, M.B.; Buren, J. Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training. Eur. J. Appl. Physiol. 2014, 114, 1463–1471. [Google Scholar] [CrossRef]
- Ellefsen, S.; Vikmoen, O.; Slettalokken, G.; Whist, J.E.; Nygaard, H.; Hollan, I.; Rauk, I.; Vegge, G.; Strand, T.A.; Raastad, T.; et al. Irisin and FNDC5: Effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women. Eur. J. Appl. Physiol. 2014, 114, 1875–1888. [Google Scholar] [CrossRef] [Green Version]
- Timmons, J.A.; Baar, K.; Davidsen, P.K.; Atherton, P.J. Is irisin a human exercise gene? Nature 2012, 488, E9–E10, discussion E10–E11. [Google Scholar] [CrossRef]
- Bonfante, I.L.P.; Chacon-Mikahil, M.P.T.; Brunelli, D.T.; Gaspari, A.F.; Duft, R.G.; Oliveira, A.G.; Araujo, T.G.; Saad, M.J.A.; Cavaglieri, C.R. Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk. Arch. Endocrinol. Metab. 2017, 61, 524–533. [Google Scholar] [CrossRef]
- Bhansali, S.; Bhansali, A.; Dhawan, V. Favourable metabolic profile sustains mitophagy and prevents metabolic abnormalities in metabolically healthy obese individuals. Diabetol. Metab. Syndr. 2017, 9, 99. [Google Scholar] [CrossRef] [Green Version]
- Gaillard, R.; Steegers, E.A.; Duijts, L.; Felix, J.F.; Hofman, A.; Franco, O.H.; Jaddoe, V.W. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: The Generation R Study. Hypertension 2014, 63, 683–691. [Google Scholar] [CrossRef] [Green Version]
- Deibert, C.; Ferrari, N.; Flock, A.; Merz, W.M.; Gembruch, U.; Lehmacher, W.; Ehrhardt, C.; Graf, C. Adipokine-myokine-hepatokine compartment-system in mothers and children: An explorative study. Contemp. Clin. Trials Commun. 2016, 3, 1–5. [Google Scholar] [CrossRef] [Green Version]
- Ferrari, N.; Bae-Gartz, I.; Bauer, C.; Janoschek, R.; Koxholt, I.; Mahabir, E.; Appel, S.; Alejandre Alcazar, M.A.; Grossmann, N.; Vohlen, C.; et al. Exercise during pregnancy and its impact on mothers and offspring in humans and mice. J. Dev. Orig. Health Dis. 2018, 9, 63–76. [Google Scholar] [CrossRef]
- Vickers, M.H.; Sloboda, D.M. Leptin as mediator of the effects of developmental programming. Best Pract. Res. Clin. Endocrinol. Metab. 2012, 26, 677–687. [Google Scholar] [CrossRef]
- Telschow, A.; Ferrari, N.; Deibert, C.; Flock, A.; Merz, W.M.; Gembruch, U.; Ehrhardt, C.; Dotsch, J.; Graf, C. High Maternal and Low Cord Blood Leptin Are Associated with BMI-SDS Gain in the First Year of Life. Obes. Facts 2019, 12, 575–585. [Google Scholar] [CrossRef]
- Boeke, C.E.; Mantzoros, C.S.; Hughes, M.D.; Rifas-Shiman, S.; Villamor, E.; Zera, C.A.; Gillman, M.W. Differential associations of leptin with adiposity across early childhood. Obesity 2013, 21, 1430–1437. [Google Scholar] [CrossRef] [Green Version]
- Hassink, S.G.; Sheslow, D.V.; de Lancey, E.; Opentanova, I.; Considine, R.V.; Caro, J.F. Serum leptin in children with obesity: Relationship to gender and development. Pediatrics 1996, 98, 201–203. [Google Scholar]
- Marino-Ortega, L.A.; Molina-Bello, A.; Polanco-Garcia, J.C.; Munoz-Valle, J.F.; Salgado-Bernabe, A.B.; Guzman-Guzman, I.P.; Parra-Rojas, I. Correlation of leptin and soluble leptin receptor levels with anthropometric parameters in mother-newborn pairs. Int. J. Clin. Exp. Med. 2015, 8, 11260–11267. [Google Scholar]
- Simpson, J.; Smith, A.D.; Fraser, A.; Sattar, N.; Lindsay, R.S.; Ring, S.M.; Tilling, K.; Davey Smith, G.; Lawlor, D.A.; Nelson, S.M. Programming of Adiposity in Childhood and Adolescence: Associations With Birth Weight and Cord Blood Adipokines. J. Clin. Endocrinol. Metab. 2017, 102, 499–506. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karege, F.; Schwald, M.; Cisse, M. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci. Lett. 2002, 328, 261–264. [Google Scholar] [CrossRef]
- Pan, W.; Banks, W.A.; Fasold, M.B.; Bluth, J.; Kastin, A.J. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998, 37, 1553–1561. [Google Scholar] [CrossRef]
- Lommatzsch, M.; Zingler, D.; Schuhbaeck, K.; Schloetcke, K.; Zingler, C.; Schuff-Werner, P.; Virchow, J.C. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol. Aging 2005, 26, 115–123. [Google Scholar] [CrossRef] [PubMed]
- Flock, A.; Weber, S.K.; Ferrari, N.; Fietz, C.; Graf, C.; Fimmers, R.; Gembruch, U.; Merz, W.M. Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum. Psychoneuroendocrinology 2016, 63, 191–197. [Google Scholar] [CrossRef]
- Camargos, A.C.; Mendonca, V.A.; Andrade, C.A.; Oliveira, K.S.; Tossige-Gomes, R.; Rocha-Vieira, E.; Neves, C.D.; Vieira, E.L.; Leite, H.R.; Oliveira, M.X.; et al. Neuroendocrine Inflammatory Responses in Overweight/Obese Infants. PLoS ONE 2016, 11, e0167593. [Google Scholar] [CrossRef]
- Walsh, J.J.; D’Angiulli, A.; Cameron, J.D.; Sigal, R.J.; Kenny, G.P.; Holcik, M.; Doucette, S.; Alberga, A.S.; Prud’homme, D.; Hadjiyannakis, S.; et al. Changes in the Brain-Derived Neurotrophic Factor Are Associated with Improvements in Diabetes Risk Factors after Exercise Training in Adolescents with Obesity: The HEARTY Randomized Controlled Trial. Neural Plast. 2018, 2018, 7169583. [Google Scholar] [CrossRef] [Green Version]
- Mora-Gonzalez, J.; Migueles, J.H.; Esteban-Cornejo, I.; Cadenas-Sanchez, C.; Pastor-Villaescusa, B.; Molina-Garcia, P.; Rodriguez-Ayllon, M.; Rico, M.C.; Gil, A.; Aguilera, C.M.; et al. Sedentarism, Physical Activity, Steps, and Neurotrophic Factors in Obese Children. Med. Sci. Sports Exerc. 2019, 51, 2325–2333. [Google Scholar] [CrossRef]
- Aksu, I.; Baykara, B.; Ozbal, S.; Cetin, F.; Sisman, A.R.; Dayi, A.; Gencoglu, C.; Tas, A.; Buyuk, E.; Gonenc-Arda, S.; et al. Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life. Neurosci. Lett. 2012, 516, 221–225. [Google Scholar] [CrossRef]
- Parnpiansil, P.; Jutapakdeegul, N.; Chentanez, T.; Kotchabhakdi, N. Exercise during pregnancy increases hippocampal brain-derived neurotrophic factor mRNA expression and spatial learning in neonatal rat pup. Neurosci. Lett. 2003, 352, 45–48. [Google Scholar] [CrossRef] [PubMed]
- Bae-Gartz, I.; Janoschek, R.; Kloppe, C.S.; Vohlen, C.; Roels, F.; Oberthur, A.; Alejandre Alcazar, M.A.; Lippach, G.; Muether, P.S.; Dinger, K.; et al. Running Exercise in Obese Pregnancies Prevents IL-6 Trans-signaling in Male Offspring. Med. Sci. Sports Exerc. 2016, 48, 829–838. [Google Scholar] [CrossRef] [PubMed]
- Hosick, P.; McMurray, R.; Hackney, A.C.; Battaglini, C.; Combs, T.; Harrell, J. Resting IL-6 and TNF-alpha level in children of different weight and fitness status. Pediatr. Exerc. Sci. 2013, 25, 238–247. [Google Scholar] [CrossRef]
- Garces, M.F.; Peralta, J.J.; Ruiz-Linares, C.E.; Lozano, A.R.; Poveda, N.E.; Torres-Sierra, A.L.; Eslava-Schmalbach, J.H.; Alzate, J.P.; Sanchez, A.Y.; Sanchez, E.; et al. Irisin levels during pregnancy and changes associated with the development of preeclampsia. J. Clin. Endocrinol. Metab. 2014, 99, 2113–2119. [Google Scholar] [CrossRef] [Green Version]
- Briana, D.; Malamitsi-Puchner, A.; Boutsikou, M.; Baka, S.; Ristani, A.; Hassiakos, D.; Gourgiotis, D.; Boutsikou, T. Myokine Irisin is Down-regulated In Fetal Growth Restriction. Arch. Dis. Child 2014, 99 (Suppl. 2), 126. [Google Scholar] [CrossRef] [Green Version]
- Okdemir, D.; Hatipoglu, N.; Kurtoglu, S.; Siraz, U.G.; Akar, H.H.; Muhtaroglu, S.; Kutuk, M.S. The Role of Irisin, Insulin and Leptin in Maternal and Fetal Interaction. J. Clin. Res. Pediatr. Endocrinol. 2018, 10, 307–315. [Google Scholar] [CrossRef]
- Gherlan, I.; Vladoiu, S.; Alexiu, F.; Giurcaneanu, M.; Oros, S.; Brehar, A.; Procopiuc, C.; Dumitrache, C. Adipocytokine profile and insulin resistance in childhood obesity. Maedica (Buchar) 2012, 7, 205–213. [Google Scholar]
- Wang, Q.; Yin, J.; Xu, L.; Cheng, H.; Zhao, X.; Xiang, H.; Lam, H.S.; Mi, J.; Li, M. Prevalence of metabolic syndrome in a cohort of Chinese schoolchildren: Comparison of two definitions and assessment of adipokines as components by factor analysis. BMC Public Health 2013, 13, 249. [Google Scholar] [CrossRef] [Green Version]
- Gonzalez-Gil, A.M.; Peschard-Franco, M.; Castillo, E.C.; Gutierrez-DelBosque, G.; Trevino, V.; Silva-Platas, C.; Perez-Villarreal, L.; Garcia-Rivas, G.; Elizondo-Montemayor, L. Myokine-adipokine cross-talk: Potential mechanisms for the association between plasma irisin and adipokines and cardiometabolic risk factors in Mexican children with obesity and the metabolic syndrome. Diabetol. Metab. Syndr. 2019, 11, 63. [Google Scholar] [CrossRef] [Green Version]
- Peiris, H.N.; Salomon, C.; Payton, D.; Ashman, K.; Vaswani, K.; Chan, A.; Rice, G.E.; Mitchell, M.D. Myostatin is localized in extravillous trophoblast and up-regulates migration. J. Clin. Res. Pediatr. Endocrinol. 2014, 99, E2288–E2297. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peiris, H.N.; Lappas, M.; Georgiou, H.M.; Vaswani, K.; Salomon, C.; Rice, G.E.; Mitchell, M.D. Myostatin in the placentae of pregnancies complicated with gestational diabetes mellitus. Placenta 2015, 36, 1–6. [Google Scholar] [CrossRef] [PubMed]
- De Zegher, F.; Perez-Cruz, M.; Diaz, M.; Gomez-Roig, M.D.; Lopez-Bermejo, A.; Ibanez, L. Less myostatin and more lean mass in large-born infants from nondiabetic mothers. J. Clin. Res. Pediatr. Endocrinol. 2014, 99, E2367–E2371. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ruiz-Casado, A.; Martin-Ruiz, A.; Perez, L.M.; Provencio, M.; Fiuza-Luces, C.; Lucia, A. Exercise and the Hallmarks of Cancer. Trends Cancer 2017, 3, 423–441. [Google Scholar] [CrossRef]
- Kyu, H.H.; Bachman, V.F.; Alexander, L.T.; Mumford, J.E.; Afshin, A.; Estep, K.; Veerman, J.L.; Delwiche, K.; Iannarone, M.L.; Moyer, M.L.; et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: Systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ 2016, 354, i3857. [Google Scholar] [CrossRef] [Green Version]
- Holloszy, J.O. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J. Biol. Chem. 1967, 242, 2278–2282. [Google Scholar]
- Cruz-Jentoft, A.J.; Bahat, G.; Bauer, J.; Boirie, Y.; Bruyere, O.; Cederholm, T.; Cooper, C.; Landi, F.; Rolland, Y.; Sayer, A.A.; et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 2019, 48, 16–31. [Google Scholar] [CrossRef] [Green Version]
German Physical Activity Recommendations for Adults |
---|
|
|
|
|
|
|
Name | Effects—Skeletal Muscle | Effects—Adipose Tissue |
---|---|---|
Adipo-Myokines | ||
Interleukin-6 (IL-6) | Induces muscle hypertrophy, glucose uptake, glycogen breakdown, and lipolysis; anti-inflammatory effect | Increases lipolysis and free fatty acid (FFA) oxidation in adipocyte, induces adipocyte browning; pro-inflammatory effect |
Irisin/fibronectin type III domain-containing protein 5 (FNDC5) | Stimulates glucose uptake and lipid metabolism; involved in muscle growth | Induces adipocyte browning and lipolysis, stimulates glycogenesis, and reduces gluconeogenesis/lipogenesis in liver |
IL-15 | Stimulates muscle growth and glucose uptake, enhances mitochondrial activity, and exerts anti-oxidative effect | Inhibits lipid accumulation in adipose tissue through adiponectin stimulation |
β-aminoiso-butyric acid (BAIBA) | Increases mitochondrial FFA oxidation and ameliorates insulin signaling; anti-inflammatory effect | Increases mitochondria FFA oxidation and browning in adipocytes; reduces hepatic de novo lipogenesis and hepatic endoplasmic reticulum stress |
Meteorin-like hormone (Metrnl) | Causes an increase in whole-body energy expenditure; improves glucose tolerance in obese/diabetic mice | Induces adipocyte browning indirectly through regulation of eosinophils |
Leukemia inhibitory factor (LIF) | Induces muscle hypertrophy, satellite cell proliferation, regeneration after muscle damage, and glucose uptake | Inhibits adipocyte differentiation |
Myostatin | Inhibits muscle hypertrophy | Inhibits myostatin results in adipocyte lipolysis and mitochondrial lipid oxidation; accelerates osteoclast formation |
IL-7 | Regulates muscle cell development, increases migration of satellite cells | Unknown |
Myokines (main effects) | ||
Fibroblast growth factor 21 (FGF21) | Insulin-responsive myokine involved in the control of glucose homoeostasis, insulin sensitivity, and ketogenesis | Thermogenesis and fat browning in brown (BAT) and white adipose tissue (WAT); increases expression of mitochondrial uncoupling protein 1 (UCP1) and other thermogenic genes in response to cold exposure and β-adrenergic stimulation in both fat depots |
Myogenin | Transcription factor; involved in muscle development, myogenesis, and repair | Unknown |
Myonectin | Regulates whole-body fatty-acid metabolism | Links skeletal muscle to lipid metabolism adipose tissue and liver |
Brain-derived neurotrophic factor (BDNF) | Increases fat oxidation in a 5’ AMP-activated protein kinase (AMPK) -dependent fashion | Size of adipose tissue |
Monocyte chemoattractant protein-1 (MCP-1) | Recruitment of monocytes and T lymphocytes; impairs insulin signaling | Involved in low-grade inflammation |
Follistatin-like 1 (FSTL1) | Affects glucose metabolism | Correlates with body mass; cardioprotective; improves endothelial function |
Angiopoietin-like protein 4 (ANGPTL4) | Increase in FFA | Unknown |
Adipokines (main effects) | ||
Visfatin | Involved in glucose metabolism? | Reduced by exercise? |
Resistin | Unknown | Correlates with body fat mass and waist circumference; may cause endothelial dysfunction |
Leptin | Increases muscle mass by increasing myocyte cell proliferation and reducing the expression of negative regulators of muscle growth including myostatin, dystrophin, or atrophy markers muscle atrophy F-box (MAFbx) or muscle RING finger 1 (MuRF1); upregulates FNDC5 expression and enhances irisin-induced myocyte proliferation, as well as the muscle growth enhancers myogenin and myonectin; post-exercise decrease | Regulation of energy homeostasis; increases energy expenditure through the stimulation of sympathetic nerve activity in BAT |
Adiponectin | Increase fatty-acid oxidation and glucose uptake | Inhibits gluconeogenesis in liver; cardioprotective; increases insulin sensitivity |
Tumor necrosis factor alpha (TNF-α) | Reduced after training; increased after very intensive exercise in response to muscle damage; reduced by chronic exercise | Correlates with body fat mass |
Name | Effects of Physical Activity |
---|---|
Adipo-Myokines | |
IL-6 | Plasma concentration of IL-6 increases during muscular exercise. The combination of mode, intensity, and duration of the exercise determines the magnitude of the exercise-induced increase of plasma IL-6 [42]. IL-6 levels were 13.2-fold increased directly after a 35-km long-distance trail run [49]. |
Irisin/FNDC5 | Controversially discussed: Two-fold increase of circulating irisin after 10 weeks of endurance training [40] vs. no increase in irisin after 8 weeks of intermittent sprint running or after 21 weeks of combined endurance and strength training [50,51]. Reduction of circulating irisin in response to 12 weeks of combined endurance and strength training [52] vs. an increase acutely (~1.2-fold) just after acute exercise [52]. |
IL-15 | Controversially discussed: Strength/resistance training leads to an increase in IL-15 messenger RNA (mRNA) level in skeletal muscles dominated by type 2 fibers [53,54]. Short bout of endurance exercise also increases levels of IL-15 in lean subjects, as well as in overweight/obese, subjects [55]. A 2.22-fold increase in serum IL-15 levels following an acute long-distance trail run was also found by Yarcic et al. [49] In contrast, neither sprint interval training (SIT) or combined aerobic and resistance training (A + R) altered IL-15 measured 48 h after exercise in overweight type 2 diabetes (T2D) [56]. |
BAIBA | Acute aerobic exercise induces a 13% and 20% increase in R-BAIBA and S-BAIBA, respectively [57]. A chronic elevation of 17% was also observed following 20 weeks (3 days/week) of aerobic exercise in previously sedentary and healthy subjects [58]. |
Metrnl | Lack of data in human studies: Aerobic exercise/swimming (40 min on three non-consecutive days) in temperate (24–25 °C), warm (36.5–37.5 °C), and cold (16.5–17.5 °C) water leads to an increase after exercise in temperate and warm water and a significant decrease in cold water in overweight women [59]. |
LIF | Aerobic exercise and concentric muscle contractions regulate muscular LIF mRNA expression in humans and lead to an induced expression of LIF in human skeletal muscle [60]. This was also confirmed for resistance exercise [48,61]. |
Myostatin | Myostatin mRNA expression was reduced in skeletal muscle after acute and long-term exercise and was even further downregulated by acute exercise on top of 12-week training in previously sedentary men [62]. 15 units of a high-intensity circuit training (HICT) program (3×/week for 5 weeks) with own body weight induced the drop of myostatin concentration but significantly only among middle-aged women [63]. |
IL-7 | Lack of data in human studies: Cyclists show higher serum levels of IL-7 compared to less active counterparts [64]. |
Myokines (main effects) | |
FGF21 | Increase in serum FGF21 levels in runners after 2 weeks of training [65] and after an acute session of running exercise [66]. |
Myogenin | Myogenin increases after eccentric resistance training [67,68]. |
Myonectin | Controversially discussed: Aerobic moderate-intensity exercise leads to a significant reduction in the amount of myonectin in older and younger patients [69]. In contrast, Seldin et al. [44] and Poranjibar et al. [70] found an increase in myonectin expression in muscle and circulation. |
BDNF | Increase in BDNF concentrations after aerobic exercise is associated with the amount of aerobic energy required by exercise in a dose-dependent manner [71]. High-intensity and high-volume resistance training lead to elevations in BDNF concentrations [72]. |
MCP-1 | Lack of data in human studies: Low-intensity exercise (walking 10,000 steps/day, 3×/week for 8 weeks) downregulates MCP-1 [73]. |
FSTL1 | Acute sprint interval exercise, as well as acute aerobic exercise, increases FSTL1 [74,75]. |
ANGPTL4 | Controversially discussed: Increase in the gene expression of ANGPTL4 after 4 and 8 h following muscle contraction stimulated in myocytes during exercise using electrical pulse stimulus [76] vs. downregulation of ANGPTL4 in the exercised leg after acute endurance exercise [77]. |
Adipokines (main effects) | |
Visfatin | Lack of data in human studies: Circuit resistance training (3×/week with intensity at 55% of one-repetition maximum) for 8 weeks reduces levels of visfatin [78]. |
Resistin | Anaerobic exercise might decrease levels of resistin [79]. Resistance training leads to a decrease in resistin after 24 and 48 h compared with baseline and a decline in baseline and immediately after levels compared with pre-training [80]. |
Leptin | Aerobic exercise leads to lower leptin levels in different population groups (prediabetic/diabetic adults; overweight/obese adults; different age and sex) [81,82,83]. |
Adiponectin | Aerobic exercise leads to an increase of adiponectin levels in different population groups (prediabetic/diabetic adults; overweight/obese individuals) [81,82]. |
TNF-α | Only highly strenuous, prolonged exercise such as marathon running results in a small increase in the plasma concentration of TNF-α [42]. The serum level of TNF-α was significantly downregulated after eccentric resistance exercise in non-athletes [54]. |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Graf, C.; Ferrari, N. Metabolic Health—The Role of Adipo-Myokines. Int. J. Mol. Sci. 2019, 20, 6159. https://doi.org/10.3390/ijms20246159
Graf C, Ferrari N. Metabolic Health—The Role of Adipo-Myokines. International Journal of Molecular Sciences. 2019; 20(24):6159. https://doi.org/10.3390/ijms20246159
Chicago/Turabian StyleGraf, Christine, and Nina Ferrari. 2019. "Metabolic Health—The Role of Adipo-Myokines" International Journal of Molecular Sciences 20, no. 24: 6159. https://doi.org/10.3390/ijms20246159