The Effect of Exercise Trainings in the Stimulation of Brown Adipose Tissue and Transformation of White Adipose Tissue to Brite Adipose Tissue: A Review
الموضوعات : Report of Health Care
Mohsen Jafari
1
,
Mehrdad Fathi
2
,
Elham Pouryamehr
3
1 - Department of Sport Sciences, Shirvan Branch, Islamic Azad University, Shirvan, Iran
2 - Department of Exercise Physiology, Ferdowsi University of Mashhad, Mashhad, Iran
3 - Department of Sport Physiology, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran
الکلمات المفتاحية: Training, Adipose Tissue,
ملخص المقالة :
There are three types of adipose tissue in the human body: white adipose tissue (WAT), brown adipose tissue (BAT) and beige or Brite adipose tissue. In WAT, energy reserves in the form of triglyceride, while in BAT triglyceride molecules lipolyze for thermogenesis through fatty acid oxidation. A protein called uncoupling protein-1 (UCP1) is responsible for non-shivering thermogenesis in BAT. The most important activators of BAT include peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sympathetic nervous system (SNS), hypothalamic–pituitary–thyroid axis (HPT axis), endothelium, atrial natriuretic peptides, irisin, β-aminoisobutyric acid (BAIBA), Fibroblast growth factor 21 (FGF21) and interleukin-6 (IL6) that generally exert their effects through stimulation of UCP1 expression and activity. Beige adipose are among white adipose and elevation of UCP1 gene expression is the main cause of their production that atrial natriuretic peptides, PGC1α, irisin, FGF21 and BAIBA are the most stimulators of this transformation. The role of exercise in the stimulation of BAT and transformation of WAT to Brite is discussed in this study.
1. Ablove T, Binkley N, Leadley S, Shelton J, Ablove R. Body mass index continues to accurately predict percent body fat as women age despite changes in muscle mass and height. Menopause. 2015; 22 (7): 727- 730.
2. Izumiya Y, Bina HA, Ouchi N, Akasaki Y, Kharitonenkov A, Walsh K. FGF21 is an Aktregulated myokine. FEBS Lett. 2008; 582: 3805- 3810.
3. Jaafari M, Akhgar R, Mohammad- Hasanzadeh M. Comparison of effectiveness of Karate, Taekwondo and Judo training on physical fitness and cardiovascular risk factors in students of Imam Hossein University. J Mil Med. 2014; 16 (2): 83- 91.
4. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell J. 2014; 156 (1): 304- 316.
5. Collins S, Sarzani R, Bordicchia M. Coordinate control of adipose ‘browning’ and energy expenditure by b-adrenergic and natriuretic peptide signaling. Int J Obesity Suppl. 2014; 4: S17- S20.
6. Archer E, Groessl EJ, Sui X, McClain AC, Wilcox S, Hand GA, et al. An economic
analysis of traditional and technology-based approaches to weight loss. Am J Prev Med. 2012; 43: 176- 182.
7. Arruda AP, Milanski M, Velloso LA. Hypothalamic inflammation and thermogenesis: the brown adipose tissue connecetion. J Bioenerg Biomembr. 2011; 43: 53- 58.
8. Bagchi M, Kim LA, Boucher J, Walshe TE, Kahn CR, D'Amore PA. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J. 2013; 27: 3257- 3271.
9. Bizheh N, Abdollahi AR, Jaafari M, Ajam Zibad Z. Relationship between neck circumferences with cardiovascular risk factors. J Babol Univ Med Sci. 2011; 13 (1): 36- 43.
10. Bizheh N, Jaafari M. The effect of a single bout of circuit resistance exercise on homocysteine, hs-CRP and fibrinogen in sedentary middle aged men. Ir J Basic Med Sci. 2011; 14 (6): 436- 442.
11. Bizheh N, Jaafari M. Effects of regular aerobic exercise on cardiorespiratory fitness and levels of fibrinogen, fibrin D-dimer and uric acid in healthy and inactive middle aged men. J Shahrekord Univ Med Sci. 2012; 14 (3): 20- 29.
12. Bizheh N, Rashidlamir A, Zabihi AR, Jaafari M. The acute effects of strength training on inflammatory markers predicting atherosclerosis: a study on inactive middle-aged men. Tehran Univ Med J. 2011; 69 (3): 204- 209.
13. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481: 463- 468.
14. Braissant O, Wahli W. Differential expression of peroxisome proliferator activated receptor-α,-β, and-γ during rat embryonic development. Endocrinology. 1998; 139 (6): 2748- 2754.
15. Haas B, Mayer P, Jennissen K, Scholz D, Berriel Diaz M, Bloch W, et al. Protein kinase G controls brown fat cell differentiation and mitochondrial biogenesis. Sci Signal. 2009; 2: 78.
16. Hall JE, Do Carmo JM, Da Silva AA, Wang Z, Hall ME. Obesity Induced hypertension interaction of neurohumoral and renal mechanisms. Circ Res. 2015; 116 (6): 991- 1006.
17. Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, Von Schulthess GK. Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med Mol Imaging. 2002; 29: 1393- 1398.
18. Hansen D, Meeusen R, Mullens A, Dendale P. Effect of acute endurance and resistance exercise on endocrine hormones directly related to lipolysis and skeletal muscle protein synthesis in adult individuals with obesity. Sports Med. 2012; 42: 415- 431.
19. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004; 84: 277- 359.
20. Cao L, Choi EY, Liu X, Martin A, Wang C, Xu X. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011; 14: 324- 338.
21. Cypess AM, Weiner LS, Roberts-Toler C, Elia EF, Kessler SH, Kahn PA, et al. Activation of human brown adipose tissue by a b3- adrenergic receptor agonist. Cell Metab. 2015; 21: 33- 38.
22. Elias I, Franckhauser S, Ferré T, Vilà L, Tafuro S, Muñoz S, et al. Adipose tissue overexpression of vascular endothelial growth factor protects against diet-induced obesity and insulin resistance. Diabetes. 2012; 61 (7): 1801- 1813.
23. Engel H, Steinert H, Buck A, Berthold T, Huch Boni RA, Von Schulthess GK, et al.
Physiological and artifactual fluorodeoxyglucose accumulations. J Nucl Med. 1996; 37: 441- 446.
24. Fiuza-Luces C, Garatachea N, Berger NA, Lucia A. Exercise is the real polypill. Physiology. 2013; 28: 330- 358.
25. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013; 19 (10): 1252- 1263.
26. Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation. 2012; 126 (1): 126- 132.
27. Hofmann T, Elbelt U, Stengel A. Irisin as a muscle-derived hormone stimulating thermogenesis – a critical update. Peptides. 2014; 54: 89- 100.
28. Jensen-Otsu E, Ward EK, Mitchell B, Schoen JA, Rothchild K, Mitchell NS, et al. The effect of Medicaid status on weight loss, hospital length of stay, and 30-day readmission after laparoscopic Roux-en-Y gastric bypass surgery. Obes Surg. 2015; 25 (2): 295-301.
29. Kolditz CI, Langin D. Adipose tissue lipolysis. Curr Opin Clin Nutr Metab Care. 2010; 13: 377- 381.
30. Koppo K, Larrouy D, Marques MA, Berlan M, Bajzova M, Polak J, et al. Lipid mobilization in subcutaneous adipose tissue during exercise in lean and obese humans. Roles of insulin and natriuretic peptides. Am J Physiol Endocrinol Metab. 2010; 299: E258- E265.
31. Gifford A, Kullberg J, Berglund J, Towse TF, Walker RC, Avison MJ, et al. Detection of brown adipose tissue in an adult human using fat- water MRI with validation by cold-activated PET. Proc Intl Soc Mag Reson. 2013; 21: 1520.
32. Hamasaki H. The effects of exercise on natriuretic peptides in individuals without heart failure. Sports. 2016; 4: 32- 44.
33. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008; 454: 463- 469.
34. Johansson K, Neovius M, Hemmingsson E. Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014; 99 (1): 14- 23.
35. Kajimura S, Saito M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol. 2014; 76: 225- 249
36. Li G, Klein RL, Matheny M, King MA, Meyer EM, Scarpace PJ. Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats. Neurosci. 2002; 115: 879- 889.
37. Ma Y, Gao M, Sun H, Liu D. Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice. Biochim Biophys Acta. 2015; 1852: 1001- 1011.
38. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl. 2002; 1: 8- 16.
39. Lebron L, Chou AJ, Carrasquillo JA. Interesting image. Unilateral F-18 FDG uptake in the neck, in patients with sympathetic denervation. Clin Nucl Med. 2010; 35: 899- 901.
40. Macfarlane DP, Forbes S, Walker BR. Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J Endocrinol. 2008; 197 (2): 189- 204.
41. Madsen L, Pedersen LM, Lillefosse HH, Fjaere E, Bronstad I, Hao Q, et al. .UCP1 induction during recruitment of brown adipose in white adipose tissue is dependent on cyclooxygenase activity. PLoS One. 2010; 5: e11391.
42. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, et al. Irisin and
FGF21 are coldinduced endocrine activators of brown fat function in humans. Cell Metab. 2014; 19: 302- 309.
43. Leskinen T, Rinnankoski-Tuikka R, Rintala M, Seppänen-Laakso T, Pöllänen E, Alen M, et al. Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs. PLoS One. 2010; e12609.
44. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007. 293: E444- E452.
45. Moradgholi E, Jafari M, Fathei M, Hejazi K. The effect of high- intensity interval training on E-selectin and P- selectin in obese women. Ir J Endocrinol Metab. 2016; 18 (4): 279- 286.
46. Morrison SF, Nakamura K. Central neural pathways for thermoregulation. Front Biosci. 2011; 16: 74- 104.
47. Keating SE, Machan EA, O'Connor HT, Gerofi JA, Sainsbury A, Caterson ID, et al. Continuous exercise but not high intensity interval training improves fat distribution in overweight adults. J Obes. 2014; 834- 865.
48. Ogden C, Carroll M, Fryar C, Flegal K. Prevalence of obesity among adults and youth: united states, 2011-2014. NCHS Data Brief. 2015; 219: 1- 8.
49. Kim KH, Kim SH, Min YK, Yang HM, Lee JB, Lee MS. Acute exercise induces FGF21 expression in mice and in healthy humans. PLoS One. 2013; 8: e63517.
50. Mitschke MM, Hoffmann LS, Gnad T, Scholz D, Kruithoff K, Mayer P, et al. Increased cGMP promotes healthy expansion and browning of white adipose tissue. FASEB J. 2013; 27: 1621- 1630.
51. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2014; 384: 766- 781.
52. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11 (2): 85- 97.
53. Oyama C, Takahashi T, Oyamada M, Oyamada T, Ohno T, Miyashita M, et al. Serum uric acid as an obesity-related indicator in early adolescence. Tohoku J Exp Med. 2006; 209 (3): 257- 262.
54. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008; 88: 1379- 1406.
55. Pedersen BK, Fischer CP. Physiological roles of muscle-derived interleukin-6 in response to exercise. Curr Opin Clin Nutr Metab Care. 2007; 10: 265- 271.
56. Pedersen LR, Olsen RH, Jürs A, Astrup A, Chabanova E, Simonsen L, et al. A randomised trial comparing weight loss with aerobic exercise in overweight individuals with coronary artery disease: the CUT-IT trial. Eur J Prev Cardiol. 2015; 22: 1009- 1017.
57. Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011; 14: 272- 279.
58. Ortega-Molina A, Efeyan A, Lopez-Guadamillas E, Munoz-Martin M, Gomez-Lopez G, Canamero M, et al. Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab. 2012; 15: 382- 394.
59. Muir LA, Neeley CK, Meyer KA, Baker NA, Brosius AM, Washabaugh AR, et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: Correlations with diabetes in human obesity. Obesity. 2016; 24 (3): 597- 605.
60. Muise ES, Azzolina B, Kuo DW, El-Sherbeini M, Tan Y, Yuan X, et al. Adipose fibroblast growth factor 21 is up-regulated by peroxisome proliferator-
activated receptor gamma and altered metabolic states. Mol Pharmacol. 2008; 74: 403- 412.
61. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998; 92: 829- 839.
62. Rashidlamir A, Hashemi Javaheri AA, Jaafari M. The effect of regular aerobic training with weight loss on concentrations of fibrinogen and resistin in healthy and overweight men. Tehran Univ Med J. 2011; 68 (12): 710- 717.
63. Rawana JS, Morgan AS, Nguyen H, Craig SG. The relation between eating-and weight-related disturbances and depression in adolescence: a review. Clin Child Fam Psychol Rev. 2010; 13 (3): 213- 230.
64. Nicholls DG, Bernson VS, Heaton GM. The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. Experientia Suppl. 1978; 32: 89- 93.
65. Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab. 2012; 15: 395.
66. Rodriguez S, Gaunt TR, Guo Y, Zheng J, Barnes MR, Tang W, et al. Lipids, obesity and gallbladder disease in women: insights from genetic studies using the cardiovascular gene-centric 50K SNP array. Eur J Hum Genet. 2015; 24 (1): 106- 112.
67. Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Gil A, Ruiz JR. Role of exercise in the activation of brown adipose tissue. Ann Nutr Metab. 2015; 67 (1): 21- 32.
68. Reihmane D, Dela F. Interleukin-6: possible biological roles during exercise. Eur J Sport Sci. 2014; 14: 242- 250.
69. Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin–IGF axis. Trends Endocrin Met. 2006; 17 (8): 328- 336.
70. Poher AL, Altirriba J, Veyrat-Durebex C, Rohner-Jeanrenaud F. Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance. Front Physiol. 2015; 6: 4.
71. Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012; 150: 620- 632.
72. Sbarbati A, Accorsi D, Benati D, Marchetti L, Orsini G, Rigotti G, et al. Subcutaneous adipose tissue classification. Eur J Histochem. 2010; 54 (4): 48.
73. Scalzo RL, Peltonen GL, Giordano GR, Binns SE, Klochak AL, Paris HL, et al. Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training. PLoS One. 2014; 9: e90696.
74. Sellayah D, Bharaj P, Sikder D. Orexin is required for brown adipose tissue development, differentiation and function. Cell Metab. 2011; 14: 478- 490.
75. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocr Metab. 2007; 92 (3): 1023- 1033.
76. Roberts LD, Boström P, O’Sullivan JF, Schinzel RT, Lewis GD, Dejam A, 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.
77. Schulz TJ, Huang P, Huang TL, Xue R, McDougall LE, Townsend KL, et al. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature. 2013; 495: 379- 383.
78. Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, et al. Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci. 2011; 108: 143- 148.
79. Suda K. Natriuretic peptide and exercise. J Phys Fitness Sports Med. 2013; 2 (3): 333- 335.
80. Sun, K, Asterholm IW, Kusminski CM, Bueno AC, Wang ZV, Pollard JW, et al. Dichotomous effects of VEGF-A on adipose tissue dysfunction. Proc Natl Acad Sci. 2012; 109: 5874- 5879.
81. Tanofsky‐Kraff M, Yanovski SZ, Schvey NA, Olsen CH, Gustafson J, Yanovski JA. A prospective study of loss of control eating for body weight gain in children at high risk for adult obesity. Int J Eat Disorder. 2009; 42 (1): 26- 30.
82. Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008; 454: 1000- 1004.
83. Van Marken Lichtenbelt W. Brown adipose tissue and the regulation of nonshivering thermogenesis. Curr Opin Clin Nutr Metab Care. 2012; 15: 547- 552.
84. Nska A, Kmiec Z. Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiologica. 2012; 205 (2): 194- 208.
85. Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, et al. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab. 2009; 9: 99- 109.
86. Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, et al. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metab. 2011; 14: 67- 79.
87. Zafrir B. Brown adipose tissue: research milestones of a potential player in human energy balance and obesity. Horm Metab Res. 2013; 45: 774- 785.
88. Stanford KI, Middelbeek RJW, Townsend KL, An D, Nygaard EB, Hitchcox KM, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013; 123 (1): 215- 223.
89. Terezakis SA, Hunt MA, Kowalski A, McCann P, Schmidtlein CR, Reiner A, et al. FDG-positron emission tomography coregistration with computed tomography scans for radiation treatment planning of lymphoma and hematologic malignancies. Int J Radiat Oncol Biol Phys. 2011; 81: 615- 622.
90. Tiraby C, Tavernier G, Lefort C, Larrouy D, Bouillaud F, Ricquier D, et al. Acquirement of brown fat cell features by human white adipose. J Biol Chem. 2003; 278: 33370- 33376.
91. Wazir Ali H, Aslam M, Mazhar Hussein M, Aziz S, Wazir F. Effect of endurance exercise on brain natriuretic peptide (BNP). Khyber Med Univ J. 2013; 5 (2): 66- 70.
92. Whittle AJ, Vidal-Puig A. NPs – heart hormones that regulate brown fat? J Clin Invest. 2012; 122: 804- 807.
93. Zhang W, Sunanaga J, Takahashi Y, Mori T, Sakurai T, Kanmura Y, Kuwaki T. Orexin neurons are indispensable for stress-induced thermogenesis in mice. J Physiol. 2010; 588: 4117- 4129.
94. Zouhal H, Jacob C, Delamarche P, GratasDelamarche A. Catecholamines and the effects of exercise, training and gender. Sports Med. 2008; 38: 401- 423.
95. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007; 6: 38- 54.
96. Sheykhiyan N, Rahami E, Ostovan M. An investigation of the effects of aerobic exercise on serum brain natriuretic peptide and C- reactive protein in women with cardiovascular diseases. J Cardiothorac Med. 2015; 3 (4): 379- 383.
97. Shimomura Y, Honda T, Shiraki M, Murakami T, Sato J, Kobayashi H, et al. Branched-chain amino acid catabolism in exercise and liver disease. J Nutr. 2006; 136 (1 suppl): 250S- 253S.
98. Tonello C, Giordano A, Cozzi V, Cinti S, Stock MJ, Carruba MO, et al. Role of sympathetic activity in controlling the expression of vascular endothelial growth factor in brown fat cells of lean and genetically obese rats. FEBS Lett. 1999; 442: 167- 172.
99. Trajkovski M, Ahmed K, Esau CC, Stoffel M. MyomiR-133 regulates brown fat differentiation through Prdm16. Nat Cell Biol. 2012; 14: 1330- 1335.
100. Velloso LA, Torsoni MA, Araujo EP. Hypothalamic dysfunction in obesity. Rev Neurosci. 2009; 20 (5-6): 441- 449.
101. Vijgen GH, Bouvy ND, Teule GJ, Brans B, Schrauwen P, van Marken Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. Plos One. 2011; 6: e17247.
102. Van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011; 301: R285- R296.
103. Vegiopoulos A, Müller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel Diaz M, et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipose. Science. 2010; 328: 1158- 1161.
104. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009; 360: 1518- 1525.
105. Vosselman MJ, Brans B, Van der Lans AA, Wierts R, van Baak MA, Mottaghy FM, et al. Brown adipose tissue activity after a high-calorie meal in humans. Am J Clin Nutr. 2013; 98: 57- 64.
106. Wang Q, Zhang M, Xu M, Gu W, Xi Y, Qi L, et al. Brown adipose tissue activation is inversely related to central obesity and metabolic parameters in adult human. PLoS One. 2015; 10: e0123795.
107. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002; 325 (7374): 1202.
108. Agoston-Coldea L, Mocan T, Dobie L, Marginean ALupu S. The association between homocysteine level and metabolic syndrome in patients of prior myocardial infarction. Rom J Intern Med. 2010; 48: 151- 158.
109. Rodriguez M, Rosety I, Rosety M, Macias I, Cavaco R, Fernieles G, et al. A 12-week aerobic training program reduced serum C-reactive protein in women with metabolic syndrome. Arch Hellenic Med. 2008; 25 (3): 363- 366.
110. Kristin L, Peter T, Cornelia M, Wener M, Catherine M, Foster-Schubert K, et al. No reduction in C-reactive protein following a 12-month randomized controlled trial of exercise in men and women. Cancer Epidemiol Biomarkers Prev. 2008; 17 (7): 1714- 1718.
111. Hubner-Wozniak E, Ochocki P. Effects of training on resting plasma levels of homocysteine and C-reactive protein in competitive male and female wrestlers. Biomed Hum Kinetics. 2009; 1: 42- 46.
112. Mora S, Lee IM, Buring JE, Ridker PM. Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA. 2006; 1412 (12): 22-29.
113. Christopher J, Hammett M, Prapavesis H, Baldi C, Varo N, Schoenbeck U. Effects of exercise training on 5 inflammatory markers associated with cardiovascular risk. Am Heart J. 2006; 151 (2): 367.e7- e16.
114. Goldhammer E, Tanchilevitch A, Maor I, Beniamin Y, Rosenschein U, Sagiv M. Exercise training modulates cytokines activity in coronary heart disease patients. Int J Cardiol. 2005; 100 (6): 93- 99.
115. Brooks N, Layne J, Gordon P, Roubenoff R, Nelson M, Castaneda-Sceppa C. Strengthtraining improves muscle quality and insulinsensitivity in Hispanic older adults with type 2diabetes. Int J Med Sci. 2007; 4: 19- 27.
116. Genest J. C-reactive protein: risk factor, biomarker and/or therapeutic target?. Canadian J Cardiol. 2010; 26: 1- 10.
117. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115 (5): 911- 919.
118. Bruun J, Helge J, Richelsen B, Stallknecht B. Diet and exercise reduce lowgrade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. Am J Physiol Endocrin Metab. 2006; 290 (5): E961.
119. Myers J. Exercise and cardiovascular health. Circulation. 2003; 107: e2- e5.
120. Grundy SM. Primary prevention of coronary heart disease: integrating risk assessment with intervention. Circulation. 1999; 100 (9): 988- 998.
121. Belmin J. Prevention of cardiovascular disease in elderly. Press Med. 2000; 24: 1234- 1239.
