Document Type : Review Article

Authors

1 Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran.

2 Department of Physical Education and Sport Sciences, Faculty of Human Sciences, University of Kashan, Kashan, Iran

3 Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

4 Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran

5 Department of Cellular Biotechnology, Cell Sciences Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Abstract

Obesity leads to metabolic diseases, and adipose tissue considered as one of the regulator of metabolism. Recent researches has demonstrated that some stimulants cause beiging of subcutaneous adipose tissue, resulting in thermogenesis and some other features of brown adipose tissue. The activation of β3-adrenergic receptors in the adipose tissue that occurs as a result of exercise also leads to the activation of UCP1 and is one of the most effective methods to combat obesity. Becacuse exercise is known as a cheap lifestyle intervention and the benefits of using it as a non-pharmocological treaetment in improvement of metabolic diseases, including obesity, have been well illustrated, Examining the molecular mechanisms of exercise is essential. One of these molecular mechanisms is the increase in thermogenesis due to exercise, which can be caused by the release of various types of cytokines. Due to the physical activity of the UCP1, it increases as the beige process occurs in the subcutaneus white adipose tissues. Increase in various cytokines and important genes involved in this process, which occur with different types of exercises at various levels, is a promise that exercises could be considered as one of the possible treatments for obesity and metabolic syndrome.

Keywords

Main Subjects

  1. Irving BA, Still CD, Argyropoulos G. Does IRISIN Have a BRITE Future as a Therapeutic Agent in Humans? Current Obesity Reports. 2014;3:235-41.
  2. Linden MA, Pincu Y, Martin SA, Woods JA, Baynard T. Moderate exercise training provides modest protection against adipose tissue inflammatory gene expression in response to high-fat feeding. Physiological Reports. 2014;2(7):
  3. Varela-Rodriguez BM, Pena-Bello L, Juiz-Valina P, Vidal-Bretal B, Cordido F, Sangiao-Alvarellos S. FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle. Scientific reports. 2016;6:29898.
  4. Joffin N, Jaubert AM, Bamba J, Barouki R, Noirez P, Forest C. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. Adipocyte. 2015;4(2):129-34.
  5. Moreno M, Moreno-Navarrete JM, Serrano M, Ortega F, Delgado E, Sanchez-Ragnarsson C, et al. Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects. PloS One. 2015;10(4):e0124100.
  6. Marandi SM, Abadi NG, Esfarjani F, Mojtahedi H, Ghasemi G. Effects of intensity of aerobics on body composition and blood lipid profile in obese/overweight females. International Journal of preventive Medicine. 2013;4(Suppl 1):S118-25.
  7. Tsiloulis T, Watt MJ. Exercise and the Regulation of Adipose Tissue Metabolism. Progress in Molecular Biology and Translational Science. 2015;135:175-201.
  8. Lo KA, Sun L. Turning WAT into BAT: a review on regulators controlling the browning of white adipocytes. Bioscience Reports. 2013;33(5(:
  9. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. 2012;150(2):366-76.
  10. de Queiroz KB, Rodovalho GV, Guimaraes JB, de Lima DC, Coimbra CC, Evangelista EA, et al. Endurance training blocks uncoupling protein 1 up-regulation in brown adipose tissue while increasing uncoupling protein 3 in the muscle tissue of rats fed with a high-sugar diet. Nutrition Research. 2012;32(9):709-17.
  11. Ringholm S, Grunnet Knudsen J, Leick L, Lundgaard A, Munk Nielsen M, Pilegaard H. PGC-1alpha is required for exercise- and exercise training-induced UCP1 up-regulation in mouse white adipose tissue. PloS One. 2013;8(5):e64123.
  12. Rocha-Rodrigues S, Rodriguez A, Gouveia AM, Goncalves IO, Becerril S, Ramirez B, et al. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Science. 2016;165:100-8.
  13. Morton TL, Galior K, McGrath C, Wu X, Uzer G, Uzer GB, et al. Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice. Frontiers in Endocrinology. 2016;7:80.
  14. Stine RR, Shapira SN, Lim HW, Ishibashi J, Harms M, Won KJ, et al. EBF2 promotes the recruitment of beige adipocytes in white adipose tissue. Molecular Metabolism. 2016;5(1):57-65.
  15. Liu X, Rossmeisl M, McClaine J, Riachi M, Harper ME, Kozak LP. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice. The Journal of Clinical Investigation. 2003;111(3):399-407.
  16. Nakhuda A, Josse AR, Gburcik V, Crossland H, Raymond F, Metairon S, et al. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. The American Journal of Clinical Nutrition. 2016;104(3):557-65.
  17. Nygaard H, Slettalokken G, Vegge G, Hollan I, Whist JE, Strand T, et al. Irisin in blood increases transiently after single sessions of intense endurance exercise and heavy strength training. PloS One. 2015;10(3):e0121367.
  18. Kelishadi R, Minasian V, Marandi SM, Farajzadegan Z, Khalighinejad P, Shirdavani S, et al. Short-term effects of a physical activity intervention on obesity and aerobic fitness of adolescent girls. International Journal of Preventive Medicine. 2014;5(Suppl 2):S108-13.
  19. De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2013;23(6):582-90.
  20. Stanford KI, Goodyear LJ. Exercise regulation of adipose tissue. Adipocyte. 2016;5(2):153-62.
  21. Kahara T, Takamura T, Hayakawa T, Nagai Y, Yamaguchi H, Katsuki T, et al. Prediction of exercise-mediated changes in metabolic markers by gene polymorphism. Diabetes Research and Clinical Practice. 2002;57(2):105-10.
  22. Shen Y, Xu X, Yue K, Xu G. Effect of different exercise protocols on metabolic profiles and fatty acid metabolism in skeletal muscle in high-fat diet-fed rats. Obesity. 2015;23(5):1000-6.
  23. Oh KS, Kim EY, Yoon M, Lee CM. Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins. Experimental & Molecular Medicine. 2007;39(3):385-94.
  24. Reisi J, Ghaedi K, Rajabi H, Marandi SM. Can Resistance Exercise Alter Irisin Levels and Expression Profiles of FNDC5 and UCP1 in Rats? Asian Journal of Sports Medicine. 2016;7(4):e35205.
  25. Ambati S, Yu P, McKinney EC, Kandasamy MK, Hartzell D, Baile CA, et al. Adipocyte nuclei captured from VAT and SAT. BMC Obesity. 2016;3:35.
  26. Esteve Rafols M. Adipose tissue: cell heterogeneity and functional diversity. Endocrinologia y nutricion: organo de la Sociedad Espanola de Endocrinologia y Nutricion. 2014;61(2):100-12.
  27. Claria J, Nguyen BT, Madenci AL, Ozaki CK, Serhan CN. Diversity of lipid mediators in human adipose tissue depots. American Journal of Physiology Cell Physiology. 2013;304(12):C1141-9.
  28. Vissers D, Hens W, Taeymans J, Baeyens JP, Poortmans J, Van Gaal L. The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis. PloS One. 2013;8(2):e56415.
  29. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nature Medicine. 2013;19(10):1252-63.
  30. Fenzl A, Kiefer FW. Brown adipose tissue and thermogenesis. Hormone Molecular Biology and Clinical Investigation. 2014;19(1):25-37.
  31. van der Lans AA, Wierts R, Vosselman MJ, Schrauwen P, Brans B, van Marken Lichtenbelt WD. Cold-activated brown adipose tissue in human adults: methodological issues. American Journal of Physiology Regulatory, Integrative and Comparative Physiology. 2014;307(2):R103-13.
  32. Oelkrug R, Polymeropoulos ET, Jastroch M. Brown adipose tissue: physiological function and evolutionary significance. Journal of Comparative Physiology B, Biochemical, Systemic, and Environmental Physiology. 2015;185(6):587-606.
  33. Giralt M, Villarroya F. White, brown, beige/brite: different adipose cells for different functions? Endocrinology. 2013;154(9):2992-3000.
  34. Poher AL, Altirriba J, Veyrat-Durebex C, Rohner-Jeanrenaud F. Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance. Frontiers in Physiology. 2015;6:4.
  35. Yeoh BS, Vijay-Kumar M. Debugging the host browns the fat. Nature Medicine. 2015;21(12):1390-1.
  36. Sidossis LS, Porter C, Saraf MK, Borsheim E, Radhakrishnan RS, Chao T, et al. Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress. Cell Metabolism. 2015;22(2):219-27.
  37. Chaurasia B, Kaddai VA, Lancaster GI, Henstridge DC, Sriram S, Galam DL, et al. Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism. Cell Metabolism. 2016;24(6):820-34.
  38. Porter C, Malagaris I, Sidossis LS. Is the heat surrounding adipose tissue mitochondria warranted? Current Opinion in Clinical Nutrition and Metabolic Care. 2014;17(6):503-8.
  39. Zuriaga MA, Fuster JJ, Gokce N, Walsh K. Humans and mice display opposing patterns of "browning" gene expression in visceral and subcutaneous white adipose tissue depots. Frontiers in Cardiovascular Medicine. 2017;4:27.
  40. Grimpo K, Volker MN, Heppe EN, Braun S, Heverhagen JT, Heldmaier G. Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance. Journal of Lipid Research. 2014;55(3):398-409.
  41. Devlin MJ. The "Skinny" on brown fat, obesity, and bone. American journal of physical anthropology. 2015;156(Suppl 59):98-115.
  42. Divakaruni AS, Brand MD. The regulation and physiology of mitochondrial proton leak. Physiology (Bethesda, Md). 2011;26(3):192-205.
  43. Cao W, Medvedev AV, Daniel KW, Collins S. beta-Adrenergic activation of p38 MAP kinase in adipocytes: cAMP induction of the uncoupling protein 1 (UCP1) gene requires p38 MAP kinase. The Journal of Biological Chemistry. 2001;276(29):27077-82.
  44. Inokuma K, Ogura-Okamatsu Y, Toda C, Kimura K, Yamashita H, Saito Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue. Diabetes. 2005;54(5):1385-91.
  45. Peymani M, Ghaedi K, Irani S, Nasr-Esfahani MH. Peroxisome Proliferator-Activated Receptor gamma Activity is Required for Appropriate Cardiomyocyte Differentiation. Cell Journal. 2016;18(2):221-8.
  46. Zadegan FG, Ghaedi K, Kalantar SM, Peymani M, Hashemi MS, Baharvand H, et al. Cardiac differentiation of mouse embryonic stem cells is influenced by a PPAR gamma/PGC-1alpha-FNDC5 pathway during the stage of cardiac precursor cell formation. European Journal of Cell Biology. 2015;94(6):257-66.
  47. Jodeiri Farshbaf M, Ghaedi K, Megraw TL, Curtiss J, Shirani Faradonbeh M, Vaziri P, et al. Does PGC1alpha/FNDC5/BDNF elicit the beneficial effects of exercise on neurodegenerative disorders? Neuromolecular Medicine. 2016;18(1):1-15.

 

 

  1. Kazeminasab F, Marandi SM, Ghaedi K, Safaeinejad Z, Esfarjani F, Nasr-Esfahani MH. A comparative study on the effects of high-fat diet and endurance training on the PGC-1alpha-FNDC5/irisin pathway in obese and non-obese male C57BL/6 mice. Applied Physiology, Nutrition, and Metabolism. 2018;43(7):651-62.
  2. Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW, et al. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002;111(7):931-41.
  3. Vernochet C, Mourier A, Bezy O, Macotela Y, Boucher J, Rardin MJ, et al. Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metabolism. 2012;16(6):765-76.
  4. Rodriguez A, Becerril S, Ezquerro S, Mendez-Gimenez L, Fruhbeck G. Crosstalk between adipokines and myokines in fat browning. Acta Physiologica. 2017;219(2):362-81.
  5. Raschke S, Eckel J. Adipo-myokines: two sides of the same coin--mediators of inflammation and mediators of exercise. Mediators of Inflammation. 2013;2013:320724.
  6. Knudsen JG, Murholm M, Carey AL, Bienso RS, Basse AL, Allen TL, et al. Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue. PloS One. 2014;9(1):e84910.
  7. Tekin S, Erden Y, Ozyalin F, Onalan EE, Cigremis Y, Colak C, et al. Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats. Neuroscience Letters. 2018;674:136-41.
  8. Perez-Sotelo D, Roca-Rivada A, Baamonde I, Baltar J, Castro AI, Dominguez E, et al. Lack of adipocyte-fndc5/irisin expression and secretion reduces thermogenesis and enhances adipogenesis. Scientific Reports. 2017;7(1):16289.
  9. Brenmoehl J, Ohde D, Albrecht E, Walz C, Tuchscherer A, Hoeflich A. Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice. Journal of Comparative Physiology B, Biochemical, Systemic, and Environmental Physiology. 2017;187(2):361-73.
  10. Braga M, Pervin S, Norris K, Bhasin S, Singh R. Inhibition of in vitro and in vivo brown fat differentiation program by myostatin. Obesity. 2013;21(6):1180-8.
  11. Schwarz NA, McKinley-Barnard SK, Spillane MB, Andre TL, Gann JJ, Willoughby DS. Effect of resistance exercise intensity on the expression of PGC-1alpha isoforms and the anabolic and catabolic signaling mediators, IGF-1 and myostatin, in human skeletal muscle. Applied Physiology, Nutrition, and Metabolism. 2016;41(8):856-63.
  12. Kazemi The correlation of resistance exercise-induced myostatin with insulin resistance and plasma cytokines in healthy young men. Journal of Endocrinological Investigation. 2016;39(4):383-8.
  13. Garcia-Fontana B, Reyes-Garcia R, Morales-Santana S, Avila-Rubio V, Munoz-Garach A, Rozas-Moreno P, et al. Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state? Endocrine. 2016;52(1):54-62.

 

 

  1. Roberts LD, Bostrom P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A, et al. beta-Aminoisobutyric acid induces browning of white fat and hepatic beta-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metabolism. 2014;19(1):96-108.
  2. Jeremic N, Chaturvedi P, Tyagi SC. Browning of White Fat: Novel Insight Into Factors, Mechanisms, and Therapeutics. Journal of Cellular Physiology. 2017;232(1):61-8.
  3. Stranska Z, Svacina S. [Myokines - muscle tissue hormones]. Vnitrni Lekarstvi. 2015;61(4):365-8.
  4. Ost M, Coleman V, Kasch J, Klaus S. Regulation of myokine expression: Role of exercise and cellular stress. Free radical Biology & Medicine. 2016;98:78-89.
  5. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157(6):1279-91.
  6. Fain JN, Company JM, Booth FW, Laughlin MH, Padilla J, Jenkins NT, et al. Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs. Metabolism: Clinical and Experimental. 2013;62(10):1503-11.
  7. Mottillo EP, Desjardins EM, Fritzen AM, Zou VZ, Crane JD, Yabut JM, et al. FGF21 does not require adipocyte AMP-activated protein kinase (AMPK) or the phosphorylation of acetyl-CoA carboxylase (ACC) to mediate improvements in whole-body glucose homeostasis. Molecular Metabolism. 2017;6(6):471-81.
  8. Zsuga J, Tajti G, Papp C, Juhasz B, Gesztelyi R. FNDC5/irisin, a molecular target for boosting reward-related learning and motivation. Medical Hypotheses. 2016;90:23-8.
  9. Dantas WS, Murai IH, Perandini LA, Azevedo H, Moreira-Filho CA, Camara NO, et al. Acute exercise elicits differential expression of insulin resistance genes in the skeletal muscle of patients with polycystic ovary syndrome. Clinical Endocrinology. 2017.
  10. Shen Y, Zhou H, Jin W, Lee HJ. Acute exercise regulates adipogenic gene expression in white adipose tissue. Biology of Sport. 2016;33(4):381-91.
  11. Gaspar RC, Munoz VR, Kuga GK, Nakandakari S, Minuzzi LG, Botezelli JD, et al. Acute physical exercise increases leptin-induced hypothalamic extracellular signal-regulated kinase1/2 phosphorylation and thermogenesis of obese mice. Journal of Cellular Biochemistry. 2019;120(1):697-704.
  12. Dehghani M, Kargarfard M, Rabiee F, Nasr-Esfahani MH, Ghaedi K. A comparative study on the effects of acute and chronic downhill running vs uphill running exercise on the RNA levels of the skeletal muscles PGC1-alpha, FNDC5 and the adipose UCP1 in BALB/c mice. Gene. 2018;679:369-76.
  13. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8.
  14. Trevellin E, Scorzeto M, Olivieri M, Granzotto M, Valerio A, Tedesco L, et al. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes. 2014;63(8):2800-11.