UCP-3: regulação da expressão gênica no músculo esquelético e possível relação com o controle do peso corporal

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Abstract

As UCPs constituem um subgrupo das proteínas carreadoras mitocondriais que estão localizadas na membrana mitocondrial interna. Por meio da dissipação do gradiente de próton, elas desacoplam a fosforilação oxidativa e convertem combustível em calor. Foram identificadas quatro isoformas da UCP. A UCP-1 foi a primeira a ser descoberta, sendo encontrada exclusivamente no tecido adiposo marrom, a UCP-2 é encontrada em vários tecidos, a UCP-3 encontra-se no músculo esquelético em humanos e tecido adiposo marrom e músculo esquelético em roedores, enquanto a UCP-4 é expressa no cérebro. A expressão da UCP-3 no músculo esquelético e no tecido adiposo marrom pode fazer destes tecidos importantes mediadores da termogênese adaptativa. No entanto, o papel da UCP-3 quanto ao gasto de energia e como causa da obesidade ainda não passa de uma hipótese. Há evidências de que a UCP-3 seja regulada pelos substratos energéticos, tais como ácidos graxos e glicose que, ao entrarem no músculo, provocam aumento da UCP-3 e aumento no gasto de energia. Nosso objetivo nesta revisão foi descrever e discutir as informações disponíveis sobre a regulação da UCP-3, e sua possível relação com o controle do peso corporal.

Translated abstract

Uncoupling proteins constitute a subgroup of mitochondrial carrier proteins that are located in the inner mitochondrial membrane. By dissipating proton gradients, they act to uncouple respiration from oxidative phosphorylation and convert fuel to heat. Four homologous UCP isoforms have been identified. UCP-1, the first UCP to be described, is found exclusively in brown adipose tissue, UCP-2 in several tissues, UCP-3 in human skeletal muscle and rat brown adipose tissue and skeletal muscle, whereas UCP-4 is expressed in the brain. Expression of UCP-3 in the skeletal muscle and the brown adipose tissue may place these tissues as important mediators for adaptative thermogenesis. However, the role of UCP-3 in energy expenditure and as a cause of obesity has been controversial. There are evidences that UCP-3 can be regulated by energy substrates as fatty acids and glucose, by entering the muscle and stimulating UCP-3 to increase energy expenditure. Our aim in this review was to describe and discuss the available information on UCP-3 regulation and its possible relation with body weight control.

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Most cited references 44

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Differential regulation of mouse uncoupling proteins among brown adipose tissue, white adipose tissue, and skeletal muscle in chronic beta 3 adrenergic receptor agonist treatment.

H Yoshitomi, K Yamazaki, S Abe … (1998)

Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters that dissipate the proton gradient, releasing stored energy as heat, without coupling to other energy-consuming processes. Therefore, the UCPs are thought to be important determinants of the metabolic efficiency. To elucidate relationships between the UCPs expressions and insulin sensitivity improvement, we treated KK-Ay mice with beta 3 adrenergic receptor agonist for 21 days and examined the changes of the UCPs mRNA expressions in various tissues. Chronic treatment of a specific beta 3 adrenergic receptor agonist, CL316,243 (0.2 mg/kg body weight/day s.c.) markedly increased the expressions of uncoupling protein 1 (UCP1), uncoupling protein 2 (UCP2), and uncoupling protein 3 (UCP3) by 14-fold, 6-fold, and 16-fold, respectively, in the brown adipose tissue (BAT). The UCP1 and UCP3 mRNA expressions in the white adipose tissue (WAT) were also increased by 12-fold and 9-fold, respectively, but the UCP2 mRNA expression was not changed in this tissue. Interestingly, the UCP2 and UCP3 mRNA expressions were strikingly decreased in the skeletal muscle and heart. Particularly, the UCP3 mRNA expression level in the skeletal muscle was dropped to 10% of that of the saline-treated control mice, indicating that the UCPs mRNA expressions are regulated in tissue-specific ways. The concentrations of plasma insulin and circulating free fatty acid (FFA) were significantly decreased, suggesting that they correlate with the reductions of the UCP2 and UCP3 mRNA expressions in the skeletal muscle and heart. It has been thought that the UCP1 and UCP3 mRNA expressions in the BAT and WAT are mainly controlled by the hypothalamus via the sympathetic nervous system, while the levels of insulin, FFA or both may play important roles in the control of the UCP2 and UCP3 mRNA expressions in the skeletal muscle an heart.