Metabolism and Circadian Rhythms—Implications for Obesity

Obesity has become a serious public health problem and a major risk factor for the development of illnesses, such as insulin resistance and hypertension. Human homeostatic systems have adapted to daily changes in light and dark in a way that the body anticipates the sleep and activity periods. Mammals have developed an endogenous circadian clock located in the suprachiasmatic nuclei of the anterior hypothalamus that responds to the environmental light-dark cycle. Similar clocks have been found in peripheral tissues, such as the liver, intestine, and adipose tissue, regulating cellular and physiological functions. The circadian clock has been reported to regulate metabolism and energy homeostasis in the liver and other peripheral tissues. This is achieved by mediating the expression and/or activity of certain metabolic enzymes and transport systems. In return, key metabolic enzymes and transcription activators interact with and affect the core clock mechanism. In addition, the core clock mechanism has been shown to be linked with lipogenic and adipogenic pathways. Animals with mutations in clock genes that disrupt cellular rhythmicity have provided evidence for the relationship between the circadian clock and metabolic homeostasis. In addition, clinical studies in shift workers and obese patients accentuate the link between the circadian clock and metabolism. This review will focus on the interconnection between the circadian clock and metabolism, with implications for obesity and how the circadian clock is influenced by hormones, nutrients, and timed meals. (Endocrine Reviews 31: 1-24, 2010) I. Introduction II. Circadian Rhythms A. Circadian rhythms in mammals B. Circadian rhythms, well-being, and life span III. The Biological Clock A. The location of the mammalian biological clock B. The biological clock at the molecular level C. Circadian rhythms in peripheral clocks IV. The Biological Clock and Energy Homeostasis A. SCN efferents B. SCN afferents C. Effect of neuropeptides and hormones on SCN D. Circadian rhythms and metabolism E. Effect of metabolism on circadian rhythms F. Effect of feeding regimens on circadian rhythms V. The Biological Clock and Obesity A. SCN connection to adipose tissue B. Effect of circadian rhythms on lipid metabolism C. Effect of high-fat diet on circadian rhythms D. Circadian rhythms and body weight E. Clock mutations and metabolic disorders F. Sleep, shift work, and obesity VI. Summary and Conclusions