Presentation Title
Role of circadian rhythm in exercise-associated skeletal muscle metabolism
Presentation Type
Keynote Speaker
Abstract
Circadian clocks orchestrate rhythmic biological processes, including metabolism, hormone production, immunity, and behaviour. The central clock resides in the hypothalamic Suprachiasmatic Nucleus (SCN) responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from nonphotic cues such as time of feeding and exercise. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue (zeitgeber) with the ability to influence and adjust the muscle clock phase in response to exercise timing. The skeletal muscle clock has emerged as a primary contributor to metabolic health, as the coordinated expression of the core clock genes BMAL1 (Brain Muscle ARNT-Like1) and CLOCK (Circadian Locomotor Output Control Kaput), Period gene (PER1, PER2, PER3), and Cryptochrome gene (CRY1, CRY2) with the rate-limiting metabolic and muscle-specific genes MYOD1, UCP3, FBXO32/Atrogin, and MYH1(MyHC IIX) facilitates the circadian and metabolic programme that supports skeletal muscle physiology. Since the muscle clock is a significant contributor to muscle-specific gene expression- many of which are metabolism related- it has a significant role in the temporal pattern of peak expression for different key metabolic genes separating catabolic vs. anabolic processes over 24 h.
Two lipid transport genes that encode for fatty-acid binding proteins, FABP4 (CT 24.0) and FABP3 (heart/muscle isoform, CT 6.0), are expressed in a circadian manner with the highest mRNA expression in the early- and mid-inactive periods, respectively. Similarly, hexokinase-2 (HK2) gene is circadian with peak expression occurring at the beginning of the active phase (CT 12.0). Three genes (PFKFB-1,3,4) that encode phosphofructokinase-2 subunits are circadian with peak expression occurring during the mid- and late-inactive phases (CT 10.0, CT 4.5, and CT 12.0, respectively). Similar circadian oscillations have been reported in other genes of lipogenesis, lipolysis, glycolysis, and glycogenesis pathways which are potentially regulated by the endogenous molecular muscle clock. Thus, the molecular clock in the SCN together with muscle clock, regulate the transcription-translation and post-translational modifications in key metabolic pathway genes and transcription factors which are essential for bioenergetics, and development of skeletal muscle with exercise.
Role of circadian rhythm in exercise-associated skeletal muscle metabolism
Circadian clocks orchestrate rhythmic biological processes, including metabolism, hormone production, immunity, and behaviour. The central clock resides in the hypothalamic Suprachiasmatic Nucleus (SCN) responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from nonphotic cues such as time of feeding and exercise. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue (zeitgeber) with the ability to influence and adjust the muscle clock phase in response to exercise timing. The skeletal muscle clock has emerged as a primary contributor to metabolic health, as the coordinated expression of the core clock genes BMAL1 (Brain Muscle ARNT-Like1) and CLOCK (Circadian Locomotor Output Control Kaput), Period gene (PER1, PER2, PER3), and Cryptochrome gene (CRY1, CRY2) with the rate-limiting metabolic and muscle-specific genes MYOD1, UCP3, FBXO32/Atrogin, and MYH1(MyHC IIX) facilitates the circadian and metabolic programme that supports skeletal muscle physiology. Since the muscle clock is a significant contributor to muscle-specific gene expression- many of which are metabolism related- it has a significant role in the temporal pattern of peak expression for different key metabolic genes separating catabolic vs. anabolic processes over 24 h.
Two lipid transport genes that encode for fatty-acid binding proteins, FABP4 (CT 24.0) and FABP3 (heart/muscle isoform, CT 6.0), are expressed in a circadian manner with the highest mRNA expression in the early- and mid-inactive periods, respectively. Similarly, hexokinase-2 (HK2) gene is circadian with peak expression occurring at the beginning of the active phase (CT 12.0). Three genes (PFKFB-1,3,4) that encode phosphofructokinase-2 subunits are circadian with peak expression occurring during the mid- and late-inactive phases (CT 10.0, CT 4.5, and CT 12.0, respectively). Similar circadian oscillations have been reported in other genes of lipogenesis, lipolysis, glycolysis, and glycogenesis pathways which are potentially regulated by the endogenous molecular muscle clock. Thus, the molecular clock in the SCN together with muscle clock, regulate the transcription-translation and post-translational modifications in key metabolic pathway genes and transcription factors which are essential for bioenergetics, and development of skeletal muscle with exercise.