Disrupting rhythms: diet-induced obesity impairs diurnal rhythms in metabolic tissues.

Abstract

Circadian rhythms are essential processes that coordinate the timing of basic organismal functions at the molecular, cellular, and behavioral levels. Oscillations are generated by the core molecular clock, which is composed of transcriptional activators (such as Bmal1 and Clock ) and repressors (such as the Period gene family). These activators are present in many types of central and peripheral tissues, including the liver (1) and adipose tissue (2). The oscillations of the core clock then regulate the rhythmic expression of other genes, such as those involved in insulin production (3), which in turn contributes to physiological rhythms in insulin secretion (4), as well as glucose and leptin levels (5,6). Under normal conditions, these rhythms are entrained by the 24-h cycles of light exposure and feeding behavior. However, a growing body of literature has begun to link circadian misalignment with human disease, including metabolic and cardiovascular dysfunction. A study of polymorphisms in the Clock gene in humans revealed that the molecular clock may play a role in cardiovascular disease, obesity, and diabetes (7). Indeed, misalignment of environmental and endogenous rhythms, as seen in nighttime shift-workers, has revealed that this population has a higher incidence of obesity and diabetes (8). Simulated circadian misalignment mimicking shift work in humans results in disturbed metabolism as exemplified by decreased leptin, increased glucose …