Circadian regulation of metabolic homeostasis in physiology and disease

A growing body of evidence indicates that circadian dysregulation-caused by lifestyle factors such as short sleep, irregular sleep patterns, and shift work-constitutes an independent risk factor for insulin resistance, obesity, and diabetes. Mammalian circadian rhythms are orchestrated by a conserved transcription-translation feedback loop driven by core transcription factors, which also regulate metabolism-related genes in a tissue-specific manner. Moreover, feeding behavior and physical activity influence the circadian clock, highlighting a reciprocal relationship between the clock and metabolism. In this review, we discuss circadian regulation of key metabolic organs-including pancreatic β cells, skeletal muscle, liver, and adipose tissue-with a focus on molecular metabolisms, and we also highlight relevant human studies to explore the therapeutic potential of targeting the circadian clock. Further investigation into the interplay between the circadian clock and metabolism holds promise for uncovering novel mechanisms and identifying innovative strategies to restore or enhance metabolic homeostasis.