Skeletal muscle mitochondrial uncoupling, adaptive thermogenesis and energy expenditure

Abstract

IntroductionIn this review we set out to give an overview of the latest developments in the field of increasing whole-body energy expenditure via adaptive thermogenesis. In particular, we focus on the contribution of skeletal muscle mitochondrial uncoupling to whole-body energy expenditure and adaptive thermogenesis. In addition, we review the latest developments regarding the application of increasing adaptive thermogenesis to fight the obesity epidemic and the possibilities to achieve this goal by modulation of skeletal muscle mitochondrial uncoupling.In the modern Western society, the prevalence of obesity and obesity-related disorders are rising. The development of obesity is the result of a prolonged imbalance between energy intake and energy expenditure, and classically focus has been on reducing energy intake to correct this imbalance. However, although successful in the short term, the success rate of reducing energy intake in the long term is notoriously poor in humans, possibly due to the decrease in resting metabolic rate and exerciserelated energy expenditure as well as by promoting an unfavourable energy intake pattern [1 ,2 ,3 ]. The reduction in metabolic rate could be a risk factor for weight regain in itself, although the contribution of energy intake and expenditure to weight gain are still under debate [4 ]. Attempts to improve energy balance by exercise programmes have generated unclear results. Structured physical activity has been reported to increase total energy expenditure rates [5] but was found not to affect energy expenditure in another study [6]. Interestingly, Turner et al. [7 ] demonstrated that a 6-month progressive exercise programme does result in weight loss but the absolute reduction is less than expected due to an increase in energy intake. This stresses the importance to measure and report both sides of the energy balance. Thus, despite the obvious social and health benefits, the limited potency for physical exercise programmes to increase total energy expenditure may be due to the fact that the caloric cost per Purpose of review The prevalence of obesity is still increasing, despite obesity treatment strategies that aim at reducing energy intake. In addition to this, exercise programmes designed to increase energy expenditure have only a low efficiency and have generated mixed results. Therefore, strategies based on increasing energy expenditure via nonexercise means are currently under investigation. One novel strategy is the modulation of adaptive thermogenesis. Recent findings Among others, adaptive thermogenesis can be modulated by changing dietary composition, treatment with hormone mimetics as well as by cold exposure. In humans, a large part of the adaptive thermogenic response is, in addition to a putative role of brown adipose tissue, determined by the skeletal muscle mass via the process of mitochondrial uncoupling. Here, we describe the molecular processes involved in mitochondrial uncoupling, state-of-the-art techniques to measure mitochondrial uncoupling ...

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“…Skeletal muscle accounts for ϳ40% of the total body mass and 20 -30% of overall oxygen consumption at rest (38,42). In addition, UCP3-mediated thermogenesis in skeletal muscle has been shown to contribute to energy expenditure (6,20,38).…”

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