The Effects of Light at Night on Circadian Clocks and Metabolism

Most organisms display endogenously produced 24-hour fluctuations in physiology and behavior, termed circadian rhythms. Circadian rhythms are driven by a transcriptional-translational feedback loop that is hierarchically expressed throughout the brain and body, with the suprachiasmatic nucleus of the hypothalamus serving as the master circadian oscillator at the top of the hierarchy. Appropriate circadian regulation is important for many homeostatic functions including energy regulation. Multiple genes involved in nutrient metabolism display rhythmic oscillations, and metabolically related hormones such as glucagon, insulin, ghrelin, leptin, and corticosterone are released in a circadian fashion. Mice harboring mutations in circadian clock genes alter feeding behavior, endocrine signaling, and dietary fat absorption. Moreover, misalignment between behavioral and molecular circadian clocks can result in obesity in both rodents and humans. Importantly, circadian rhythms are most potently synchronized to the external environment by light information and exposure to light at night potentially disrupts circadian system function. Since the advent of electric lights around the turn of the 20th century, exposure to artificial and irregular light schedules has become commonplace. The increase in exposure to light at night parallels the global increase in the prevalence of obesity and metabolic disorders. In this review, we propose that exposure to light at night alters metabolic function through disruption of the circadian system. We first provide an introduction to the circadian system, with a specific emphasis on the effects of light on circadian rhythms. Next we address interactions between the circadian system and metabolism. Finally, we review current experimental and epidemiological work directly associating exposure to light at night and metabolism. (Endocrine Reviews 35: 648 -670, 2014) I. Introduction II. Circadian Clockwork A. The suprachiasmatic nucleus is the master circadian oscillator B. Molecular mechanisms of the circadian clock C. Additional clocks persist outside the SCN D. Diurnality versus nocturnality E. Light entrains the circadian system F. Light at night and the circadian system III. The Bidirectional Regulation Between Circadian Systems and Metabolism A. Knocking out the circadian clock and obesity B. Metabolism and the circadian clock are reciprocally related C. You are what when you eat? IV. Exposure to Light at Night and Obesity A. Evidence from nonhuman animals B. Evidence in humans V. Additional Pathways Through Which Light Affects Metabolism A. Melatonin and metabolism B. Glucocorticoids and metabolism C. Sleep and metabolism VI. Implications and Interventions VII. Conclusions