Regulação da expressão gênica das UCP2 e UCP3 pela restrição energética, jejum e exercício físico
Palabras clave:
dieta com restrição de proteínas, expressão gênica, exercício, gordura marrom, jejum, UCP2, UCP3Resumen
O tecido adiposo marrom, onde se localiza a proteína desacopladora 1 (UCP1 - uncoupling protein 1), é um tecido termogênico presente somente nos pequenos mamíferos e neonatos, com função de manter temperatura e peso corporal estáveis quando da exposição ao frio ou consumo de dietas hipercalóricas. Como a UCP1 está localizada exclusivamente no tecido adiposo marrom, tecido pouco expressado em adultos, os estudos dão ênfase às proteínas desacopladoras 2 e 3 (UCP2 e UCP3), proteínas homólogas à UCP1, expressas em múltiplos tecidos e nos músculos esqueléticos, respectivamente. A atividade física provoca aumento do RNAm da UCP2 e UCP3, questiona-se, porém, se este aumento é devido a mudanças no metabolismo de gordura ou a mudanças no metabolismo energético. Durante a restrição energética ou jejum, há depleção de gordura corporal e aumento da concentração plasmática de ácidos graxos livres, com regulação positiva da UCP2 e da UCP3 no músculo e aumento da oxidação lipídica. A concentração elevada de ácidos graxos representa sinal intracelular importante na indução da expressão das UCP no músculo, o que pode estar ligado à sua utilização como combustível até que ocorra aumento da demanda do organismo para dissipação da energia. No entanto, discute-se se a UCP2 e a UCP3 no músculo esquelético têm como função mediar a termogênese ou regular a oxidação de lipídios.
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Ricquier D, Casteilla L, Bouillaud F. Molecular studies of the uncoupling protein. FASEB J. 1991; 5(9):2237-42
Harrold JA, Widdowson PS, Clapham JC, Williams G. Individual severity of obesity in unselected Wistar rats: relationship with hyperphagia. Am J Physiol Endocrinol Metab. 2000; 279(2): E340-E347.
Millet L, Vidal H, Andrielli F, Larrouy D, Rion JP, Ricquier D, et al. Increased uncoupling protein-2 and-3 mRNA expression during fasting in obese and lean humans. J Clin Invest. 1997; 100(11): 2665-70.
Ricquier D, Bouillaud F. Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. J Physiol. 2000; 529(Pt1):3-10
Matamala JC, Gianotti M, Pericás J, Quevedo S, Roca P, Palou A, et al. Changes induced by fasting and dietetic obesity in thermogenic parameters of rat brown adipose tissue mitochondrial subpopulations. Biochem J. 1996; 319(Pt2): 529-34.
Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science. 1999; 283(5399): 212-4.
Margareto J, Marti A, Martinez JA. Changes in UCP mRNA expression levels in brown adipose tissue and skeletal muscle after feeding a high-energy diet and relationships with leptin, glucose and PPARgamma. J Nutr Biochem. 2001; 12(3):130-7.
Schrauwen P, Hesselink M. UCP2 and UCP3 in muscle controlling body metabolism. J Exp Biol. 2002; 205(Pt15):2275-85.
Ceddia RB, Willian WN, Jr Lima FB, Flandin P, Curi R, Giacobino JP. Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocyte. Eur J Biochem. 2000; 267(19):5952-8
Orci L, Cook WS, Ravazzola M, Purelet A, Eng WS, Di Liberto M, et al. Rapid transformation of white adipocytes into fat-oxidizing machines. Proc Natl Acad Sci USA. 2004; 101(7):2058-63.
Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nature Genet. 1997; 15(3): 269-72.
Boss O, Samec S, Paoloni-Giacobino A, Rossier C, Sullo A, Seydoux V, et al. Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett. 1997; 408(1):39-42
Tsuboyama-Kasaoka N, Ezaki O. Mitochondrial uncoupling proteins 3 (UCP3) in skeletal muscle. Front Biosc. 2001; 1(6):570-4
Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB. UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun. 1997; 235(1):79-82.
Argilés JM, Busquets S, López-Soriano FJ. The role of uncoupling proteins in pathophysiological states. Biochem Biophys Res Commun. 2002; 293(4):1145-52
Samec S, Seydoux J, Dullo AG. Interorgan signaling between adipose tissue metabolism and skeletal muscle uncoupling protein homologs: is there a role for circulating free fatty acids? Diabetes. 1998; 47(11):1693-8.
Schrauwen P, Walder K, Ravussin E. Human uncoupling proteins and obesity. Obes Res. 1999; 7(1):97-105.
Weigle DS, Selfridge LE, Schwarts MW, Seeley RJ, Cumming DE, Havel PJ, et al. Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting. Diabetes. 1998; 47(2):298-302.
Rial E, González-Barroso MM. Physiological regulation of the transport activity in the uncoupling proteins UCP1 and UCP2. Biochim Biophys Acta. 2001; 1504(1):70-81.
Nordfors L, Hoffstedt J, Nyberg B, Thome A, Arner P, Schalling M, et al. Reduced gene expression of UCP2 but not UCP3 in skeletal muscle of human obese subjects. Diabetologia. 1998; 41(8): 935-9.
Ricquier D, Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J. 2000; 345(Pt2):161-79.
Hesselink MKC, Mensink M, Schrauwen P. Human uncoupling protein-3 and obesity: an update. Obes Res. 2003; 11(12):1429-43.
Boss O, Hagen T, Lowell BB. Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes. 2000; 49(2): 143-56.
Zhou M, Lin BZ, Coughlin S, Vallega G, Pilch PF. UCP3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase. Am J Physiol. 2000; 279(3):E622-E629.
Abu-Elheiga L, Oh W, Kordari P, Wakil SJ. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci USA. 2003; 100(18):10207-12.
Schrauwen P, Hesselink MK, Vaartjes I, kornips E, Saris WH, Giacobino JP, et al. Effect of acute exercice on uncoupling protein 3 is a fat metabolism- -mediated effect. Am J Physiol. 2001; 282(1): E11-E17.
Dulloo AG, Samec S, Seydoux J. Uncoupling protein 3 and fatty acid metabolism. Biochem Soc Trans. 2001; 29(Pt6):785-91
Laughlin MH, Simpson T, Sexton WL, Brown OR, Smith JK, Korthuis RJ. Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training. J Appl Physiol. 1990; 68(6):2337-43.
Samec S, Seydoux J, Russel AP, Montani JP, Dulloo AG. Skeletal muscle heterogeneity in fasting- -induced upregulation of genes encoding UCP2, UCP3, PPARgamna and key enzymes of lipid oxidation. Pflugers Arch. 2002; 445(1):80-6.
Pedersen SB, Borgeum JD, Kristensen K, Norrelund H, Otto J, Jorgensen L, et al. Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans. Int J Obes Metab Disord. 2000; 24(8):968-75.
Simoneau JA, Kelley DE, Neverova M, Warden CH. Overexpression of muscle uncoupling protein 2 content in human obesity associates with reduced skeletal muscle lipid utilization. FASEB J. 1998; 12(15):1739-45.
Oberkofler H, Liu YM, Esterbauer H, Hell E, Krempler F, Patsch W. Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese human. Diabetologia. 1998; 41(8): 940-6.
Boss O, Samec S, Desplanches D, Mayet MH, Seydoux J, Muzzin P, et al. Effect of endurance training on mRNA expression of uncoupling proteins 1, 2 and 3 in the rat. FASEB J. 1998; 12(3):335-9.
Lentes KU, Tu N, Chen H, Winnikes U, Reinert I, Marmann G, et al. Genomic organization and mutational analysis of the human UCP2 gene a prime candidate gene for human obesity. J Recept Signal Transduct Res. 1999; 19(1-4):229-44.
Noland RC, Hickner RC, Jimenez-Linan M, VidalPuig A, Zheng D, et al. Acute endurance exercise increases skeletal muscle uncoupling protein-3 gene expression in untrained but not trained humans. Metabolism. 2003; 52(2):152-8.
Samec S, Seydoux J, Dullo AG. Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: a link with insulin resistance. Diabetes. 1999; 48(2):436-41.
Gong D, He Y, Karas M, Reitman M. Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists and leptin. J Biol Chem. 1997; 272(39): 24129-32
de Lange P, Lanni A, Beneduce L, Moreno M, Lombardi A, Silvestri E, et al. Uncoupling protein3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology. 2001; 142(8):3414-20
Lanni A, Moreno M, Lombardi A, Goglia F. Thyroid hormone and uncoupling proteins. FEBS Lett. 2003; 543(1-3):5-10.
Schrauwen P & Hesselink M. Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited. Proc Nutr Soc. 2003; 62(3):635-43.
Tonkonogi M, Krook A, Walsh B, Sahlin K. Endurance training increases stimulation of uncoupling of skeletal muscle mitochondria in humans by non-esterified fatty acids: an uncoupling-protein-mediated effect? Biochem J. 2000; 351(Pt3):805-10.
Tsuboyama-Kasaoka N, Tsunoda N, Maruyama K, Takahashi M, Kim H, Ikemote S, et al. Upregulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down-regulation of UCP3 by denervation in skeletal muscle. Biochem Biophys Res Commun. 1998; 247(2):498-503.
Newsholme EA, Leech AR. Biochemistry for the medical sciences. New York: John Wiley & Sons. 1995.
Cortright RN, Zheng D, Jones JP, Fluckey JD, DiCarlo SE, Grujic D, et al. Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation. Am J Physiol. 1999; 276(1 Pt1):E217-E221.
Pilegaard H, Ordway GA, Saltin B, Neufer PD. Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercice. Am J Physiol Endocrinal Metab. 2000; 279(4):E806-14.
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Derechos de autor 2023 Renata Polessi BOSCHINI, Jair Rodrigues GARCIA JÚNIOR
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
