![]() ![]() In rodent studies, clock gene mutants often display obese or diabetic phenotypes and possess defects in core metabolic pathways such as insulin secretion and gluconeogenesis. In addition to evidence of circadian rhythms in metabolism, data increasingly suggest that disruption of the circadian system increases the risk of metabolic diseases. The aggregate effect is that an array of metabolic processes-including insulin sensitivity, insulin secretion, cholesterol synthesis, fat oxidation, and energy expenditure-all follow a rhythm across the 24-hour day. This system of clocks collectively modulates a wide array of metabolic targets, such as glucocorticoids, the master energy sensor AMPK, rate-limiting steps in fatty acid and cholesterol synthesis, and hepatic CREB to modulate gluconeogenesis. The circadian system comprises a central pacemaker in the brain and a series of clocks in peripheral tissues throughout the body, including liver, muscle, and adipose tissue. These interconnections among the circadian system, metabolism, and behavior underscore the importance of chronobiology for preventing and treating diabetes, obesity, and hyperlipidemia. We therefore also review evidence that circadian misalignment induced by mistimed light exposure, sleep, or food intake adversely affects metabolic health in humans. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. Several of these rhythms peak in the biological morning or early afternoon, implicating earlier in the daytime as optimal for food intake. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. The circadian system orchestrates metabolism in daily 24-hour cycles. ![]()
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