Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis

Abstract

While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation is specific to exercise at the active phase. At the molecular level, HIF1a, a central regulator of glycolysis during hypoxia, is selectively activated in a time-dependent manner upon exercise, resulting in carbohydrate exhaustion, usage of alternative energy sources, and adaptation of systemic energy expenditure. Our findings demonstrate that the time of day is a critical factor to amplify the beneficial impact of exercise on both metabolic pathways within skeletal muscle and systemic energy homeostasis.

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

“…Although both endurance and resistance exercise lead to fat loss (Benito et al, 2015), resistance but not endurance exercise increases muscle mass and resting metabolic rate (Poehlman et al, 1991(Poehlman et al, , 2002Dolezal & Potteiger, 1998;Hunter et al, 2000), providing better weight loss maintenance in long-term observation. There have been numerous analyses of plasma metabolites following acute endurance exercise in both clinical and animal models (Lewis et al, 2010;Huffman et al, 2014;Aguer et al, 2017;Duft et al, 2017;Starnes et al, 2017;Sato et al, 2019), which has generated a number of metabolomics "signatures" in the circulation. These plasmas metabolic profiles provide signatures of endurance exercise performance and cardiovascular disease susceptibility and also identify molecular pathways that may modulate the salutary effects on cardiovascular function.…”

Time‐of‐day dependent effects of contractile activity on the phase of the skeletal muscle clock

“…Exercise is a well-known stimulus that can alter skeletal muscle and organismal physiology. While emerging data have shown potent time-of-day specific outcomes of exercise on skeletal muscle gene expression and metabolism (Ezagouri et al 2019;Gabriel & Zierath, 2019;Sato et al 2019), studies of the potential role of exercise as an environmental time cue for circadian clocks have been limited. Specifically, studies have performed time-of-day exercise interventions and measured both behavioural as well as clock outcomes but all these studies performed repeated exercise training (Edgar & Dement, 1991;Marchant & Mistlberger, 1996;Yamanaka et al 2008;Wolff & Esser, 2012).…”

Circadian rhythm phase shifts caused by timed exercise vary with chronotype

“…In many individuals, especially in people with a late chronotype, an advance of the internal circadian rhythm would better align internal rhythms with the environment and with standard social schedules. Recent studies in mice showed that exercise performance, gene transcription, and energy utilization depend on the time of day of exercise (31,32). Clinical studies have conflicting results, but some have shown that morning or early afternoon exercise phase advances, while evening exercise phase delays the internal circadian rhythm (21,(33)(34)(35)(36).…”