Abstract
Physical training (PT) has been considered as a treatment in metabolic syndrome (MS), since it induces thermogenic activity in brown (BAT) and white (WAT) adipose tissues. We evaluated the therapeutic effect of PT on activity of WAT and BAT in rats with MS induced by high-fat diet (30% lard) for 13 weeks and submitted, for the last 6 weeks, to swimming or kept sedentary (SED) rats. MS-SED rats compared to control diet (CT-SED) rats showed low physical fitness and high levels of glucose, insulin, homeostasis evaluation of insulin resistance (HOMA-IR), homeostasis evaluation of the functional capacity of β-cells (HOMA-β), and blood pressure. The gastrocnemius muscle decreased in peroxisome proliferator-activated receptor gamma coactivator 1-alpha and beta (PGC-1α, PGC-1β), and uncoupled protein 2 and 3 (UCP2 and UCP3) expressions. Both WAT and BAT increased in the adipocyte area and decreased in blood vessels and fibroblast numbers. WAT increased in expression of pro-inflammatory adipokines and decreased in anti-inflammatory adipokine and adiponectin. WAT and gastrocnemius showed impairment in the insulin signaling pathway. In response to PT, MS rats showed increased physical fitness and restoration of certain biometric and biochemical parameters and blood pressure. PT also induced thermogenic modulations in skeletal muscle, WAT and BAT, and also improved the insulin signaling pathway. Collectively, PT was effective in treating MS by inducing improvement in physical fitness and interchangeable effects between skeletal muscle, WAT and BAT, suggesting a development of brown-like adipocyte cells.
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Aoi W, Naito Y, Yoshikawa T (2011) Dietary exercise as a novel strategy for the prevention and treatment of metabolic syndrome: effects on skeletal muscle function. J Nutr Metab 676208
Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De Matteis R, Cinti S (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298:E1244–E1253
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP Spiegelman BM (2012) A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468
Cangussu LM, de Castro UG, do Pilar Machado R, Silva ME, Ferreira PM, dos Santos RA, Campagnole-Santos MJ, Alzamora AC (2009) Angiotensin-(1-7) antagonist, A-779, microinjection into the caudal ventrolateral medulla of renovascular hypertensive rats restores baroreflex bradycardia. Peptides 30:1921–1927
Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359
Choi SW, Claycombe KJ, Martinez JA, Friso S, Schalinske KL (2013) Nutritional epigenomics: a portal to disease prevention. Adv Nutr 4:530–532
de Castro UG, dos Santos RA, Silva ME, de Lima WG, Campagnole-Santos MJ, Alzamora AC (2013) Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats. Lipids Health Dis 12:136
De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R (2013) Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis 23:582–590
de Queiroz KB, Coimbra RS, Ferreira AR, Carneiro CM, Paiva NC, Costa DC, Evangelista EA, Guerra-Sá R (2014) Molecular mechanism driving retroperitoneal adipocyte hypertrophy and hyperplasia in response to a high-sugar diet. Mol Nutr Food Res 58:2331–2341
Giordano A, Frontini A, Cinti S (2016) Convertible visceral fat as a therapeutic target to curb obesity. Nat Rev Drug Discov 15:405–424
Gong CX, Grundke-Iqbal I, Iqbal K (2010) Targeting tau protein in Alzheimer’s disease. Drugs Aging 27:351–365
Hajer GR, van Haeften TW, Visseren FL (2008) Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 29:2959–2971
Handschin C, Spiegelman BM (2008) The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 454:463–469
Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263
Hatano D, Ogasawara J, Endoh S, Sakurai T, Nomura S, Kizaki T, Ohno H, Komabayashi T, Izawa T (2011) Effect of exercise training on the density of endothelial cells in the white adipose tissue of rats. Scand J Med Sci Sports 21:e115–e121
Janani C, Ranjitha Kumari BD (2015) PPAR gamma gene—a review. Diabetes Metab Syndr 9:46–50
Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T (1999) PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4:597–609
Levin BE (1992) Intracarotid glucose induced norepinephrine response and the development of diet induced obesity. Int J Obes Relat Metab Disord 16:451–457
Lozano I, Van der Werf R, Bietiger W, Seyfritz E, Peronet C, Pinget M, Jeandidier N, Maillard E, Marchioni E, Sigrist S, Dal S (2016) High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutr Metab (Lond) 13:15
Ma X, Lee P, Chisholm DJ, James DE (2015) Control of adipocyte differentiation in different fat depots; implications for pathophysiology or therapy. Front Endocrinol (Lausanne) 6:1
Maia RC, Sousa LE, Santos RA, Silva ME, Lima WG, Campagnole-Santos MJ, Alzamora AC (2015) Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats. Braz J Med Biol Res 48:1010–1022
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Nicholls DG (2001) A history of UCP1. Biochem Soc Trans 29:751–755
Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD (2009) Pasinetti GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 66:352–361
Raper JA, Love LK, Paterson DH, Peters SJ, Heigenhauser GJ, Kowalchuk JM (2014) Effect of high-fat and high-carbohydrate diets on pulmonary O2 uptake kinetics during the transition to moderate-intensity exercise. J Appl Physiol (1985) 117:1371–1379
Reeves PG (1997) Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127:838S–841S
Rodrigues MC, Campagnole-Santos MJ, Machado RP, Silva ME, Rocha JL, Ferreira PM, Santos RA, Alzamora AC (2007) Evidence for a role of AT(2) receptors at the CVLM in the cardiovascular changes induced by low-intensity physical activity in renovascular hypertensive rats. Peptides 28:1375–1382
Roopchand DE, Carmody RN, Kuhn P, Moskal K, Rojas-Silva P, Turnbaugh PJ, Raskin I (2015) Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes 64:2847–2858
Rowland LA, Bal NC, Periasamy M (2015) The role of skeletal-muscle-based thermogenic mechanisms in vertebrate endothermy. Biol Rev Camb Philos Soc 90:1279–1297
Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Gil Á, Ruiz JR (2015) Role of exercise in the activation of Brown adipose tissue. Ann Nutr Metab 67:21–32
Schnyder S, Handschin C (2015) Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone 80:115–125
Slocum N, Durrant JR, Bailey D, Yoon L, Jordan H, Barton J, Brown RH, Clifton L, Milliken T, Harrington W, Kimbrough C, Faber CA, Cariello N, Elangbam CS (2013) Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment. Exp Toxicol Pathol 65:549–557
Soares ER, Lima WG, Machado RP, Carneiro CM, Silva ME, Rodrigues MC, De Castro UG, Santos RA, Campagnole-Santos MJ, Alzamora AC (2011) Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats. Braz J Med Biol Res 44:573–582
Sousa LE, Magalhães WG, Bezerra FS, Santos RA, Campagnole-Santos MJ, Isoldi MC, Alzamora AC (2015) Exercise training restores oxidative stress and nitric oxide synthases in the rostral ventrolateral medulla of renovascular hypertensive rats. Free Radic Res 49:1335–1343
Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ (2013) Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 123:215–223
van Marken Lichtenbelt W (2012) Brown adipose tissue and the regulation of nonshivering thermogenesis. Curr Opin Clin Nutr Metab Care 15:547–552
Vargas-Robles H, Rios A, Arellano-Mendoza M, Escalante BA, Schnoor M (2015) Antioxidative diet supplementation reverses high-fat diet-induced increases of cardiovascular risk factors in mice. Oxidative Med Cell Longev 2015:467471
Werman A, Hollenberg A, Solanes G, Bjorbaek C, Vidal-Puig AJ, Flier JS (1997) Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin. J Biol Chem 272:20230–20235
Zacarias AC, Barbosa MA, Guerra-Sá R, De Castro UGM, Bezerra FS, Lima WG, Cardoso LM, Santos RAS, Campagnole-Santos MJ, Alzamora AC (2017) Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet. Redox Rep 13:1–9
Acknowledgments
The authors are grateful for support from the Center of Animal Science (CCA/UFOP), Laboratory of Biochemistry and Molecular Biology and Laboratory of Experimental Physiology. This study was supported by the Universidade Federal de Ouro Preto (UFOP), Pró-Reitoria de Pós-Graduação (PROPP-UFOP), FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais)-RedeToxifar, CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPEMIG-Universal, Pronex (FAPEMIG/ CNPq) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).
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Barbosa, M.A., Guerra-Sá, R., De Castro, U.G.M. et al. Physical training improves thermogenesis and insulin pathway, and induces remodeling in white and brown adipose tissues. J Physiol Biochem 74, 441–454 (2018). https://doi.org/10.1007/s13105-018-0637-x
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DOI: https://doi.org/10.1007/s13105-018-0637-x