In mammals, the central clock localized in the central nervous system imposes a circadian rhythmicity to all organs. This is achieved thanks to a well-conserved molecular clockwork, involving interactions between several transcription factors, whose pace is conveyed to peripheral tissues through neuronal and humoral signals. The molecular clock plays a key role in the control of numerous physiological processes and takes part in the regulation of metabolism and energy balance. Skeletal muscle is one of the peripheral organs whose function is under the control of the molecular clock. However, although skeletal muscle metabolism and performances display circadian rhythmicity, the role of the molecular clock in the skeletal muscle has remained unappreciated for years. Peripheral organs such as skeletal muscle, and the liver, among others, can be desynchronized from the central clock by external stimuli, such as feeding or exercise, which impose a new rhythm at the organism level. In this review, we discuss our current understanding of the clock in skeletal muscle circadian physiology, focusing on the control of myogenesis and skeletal muscle metabolism. Keywords: circadian molecular clock, exercise, metabolism, Rev-erb , Rev-erb , skeletal muscle
Date submitted 10 April 2015; date of final acceptance 3 May 2015
IntroductionSkeletal muscle represents 40% of the body mass and ensures locomotion, posture support and breathing. It is also a major metabolic organ that is highly sensitive to insulin.Skeletal muscle formation begins during embryogenesis, when the different muscle patterns are organized. During post-natal growth, functional muscles, which possess specific contractile and metabolic properties, are further formed. In adults, skeletal muscles are classified based on their fast and slow fibre content. Slow muscles, such as the soleus and diaphragm, consist in the majority of slow oxidative fibres, which contain high amount of mitochondria, mainly oxidize lipids and glucose and are engaged in low-intensity long-lasting endurance exercise. By contrast, fast muscles such as the extensor digitorum longus (EDL), are mainly composed of glycolytic fibres and are involved in short-duration high-intensity exercise. While the fibre type is established during post-natal development, it remains plastic and can be modulated by external stimuli. Exercise is one of the stimuli-modulating skeletal muscle properties: endurance exercise promotes slow-twitch conversion of fibres, while strength exercise favours fast-twitch conversion [1]. Beyond its effect on skeletal muscle properties, exercise acts at the whole organism level to control energy balance. Studies have indeed reported that exercise influences whole-body circadian rhythmicity [2][3][4][5].Rhythmicity is an evolutionary feature conserved from bacteria to the plant and animal kingdoms [6], and that is generated by an endogenous molecular clock. In mammals, the circadian pacemaker lies in the suprachiasmatic nucleus (SCN), located in the hypothalamus, and is referred ...