Entrainment of the mouse circadian clock: Effects of stress, exercise, and nutrition

The circadian clock system in mammals plays a fundamental role in maintaining homeostasis. Entrainment is an important characteristic of the internal clock, by which appropriate timing is maintained according to external daily stimuli, such as light, stress, exercise, and/or food. Disorganized entrainment or a misaligned clock time, such as jet lag, increases health disturbances. The central clock in the suprachiasmatic nuclei, located in the hypothalamus, receives information about arousal stimuli, such as physical stress or exercise, and changes the clock time by modifying neural activity or the expression of circadian clock genes. Although feeding stimuli cannot entrain the central clock in a normal light–dark cycle, the central clock can partially detect the metabolic status. Local clocks in the peripheral tissues, including liver and kidney, have a strong direct response to the external stimuli of stress, exercise, and/or food that is independent of the central clock. The mechanism underlying entrainment by stress/exercise is mediated by glucocorticoids, sympathetic nerves, oxidative stress, hypoxia, pH, cytokines, and temperature. Food/nutrition-induced entrainment is mediated by fasting-induced hormonal or metabolic changes and re-feeding-induced insulin or oxyntomodulin secretion. Chrono-nutrition is a clinical application based on chronobiology research. Future studies are required to elucidate the effects of eating and nutrient composition on the human circadian clock. Here, we focus on the central and peripheral clocks mostly in rodents’ studies and review the findings of recent investigations of the effects of stress, exercise, and food on the entrainment system.