Capsiate administration results in an uncoupling protein-3 downregulation, an enhanced muscle oxidative capacity and a decreased abdominal fat content in vivo

Abstract

The involvement of skeletal muscle mitochondrial uncoupling protein-3 (UCP3) in the control of energy expenditure in skeletal muscle and at the whole-body level is still a matter of debate. We previously reported that UCP3 downregulation is linked to an enhanced mitochondrial energy metabolism in rat skeletal muscle as a result of acute capsiate treatment. Here, we aimed at investigating noninvasively the effects of chronic capsiate ingestion on metabolic changes occurring in exercising gastrocnemius muscle and at the whole-body level. We used an original experimental setup allowing a complete noninvasive investigation of gastrocnemius muscle function in situ using 31-phosphorus magnetic resonance spectroscopy. Whole-body fat composition was determined using magnetic resonance imaging and UCP3 gene expression was measured by quantitative real-time RT-PCR analysis. We found that a 14-day daily administration of capsiate (100 mg kg(-1) body weight) reduced UCP3 gene expression and increased phosphocreatine level at baseline and during the stimulation period in gastrocnemius muscle. During muscle stimulation, pH(i) showed a larger alkalosis in the capsiate group suggesting a lower glycolysis and a compensatory higher aerobic contribution to ATP production. Although the capsiate-treated rats were hyperphagic as compared to control animals, they showed a lower weight gain coupled to a decreased abdominal fat content. Overall, our data indicated that capsiate administration contributes to the enhancement of aerobic ATP production and the reduction of body fat content coupled to a UCP3 gene downregulation.