The Link Between Dietary Timing and Exercise Performance Through Adipocyte AMPKα2 Signaling

Emerging evidence suggests that the timing of eating and exercise over the course of the day is paramount to metabolism and physical function. This review highlights seminal studies showing that adipocyte AMPKα2 signaling controls circadian adipose tissue-skeletal muscle communication. Day-restricted feeding has been shown to improve exercise performance via adipocyte-specific activation of AMPKα2, which controls fat-muscle crosstalk in a time-of-day dependent manner. This review also discusses corroborating experimental studies designating mesenchymal stem cells as key cellular mediators, showing that exercise in the afternoon leads to better metabolic effects in humans, and illustrating how incorrect timing of food intake leads to leptin resistance and metabolic dysregulation. Multi-omics strategies have shed light on the molecular mechanisms underlying such effects of time, showing the circadian control of metabolic processes across tissues. These results advance our knowledge of chronometabolism and offer exciting temporal intervention treatments for metabolic diseases, such as time-restricted feeding, timed exercise, and chronopharmacological targeting of AMPK. Fat-muscle crosstalk, physical performance, and metabolic health outcomes can possibly be optimized by synchronizing dietary and exercise timing with endogenous circadian rhythms.