Functional CLOCK is not essentially associated with metabolic disruption caused by sleep phase feeding in mice

Abstract

Consuming food at uncommon times during the day might be associated with obesity in experimental animals and humans. We previously reported that mice become obese and their metabolism becomes disrupted when they consume food during the daytime (sleep phase feeding; SPF), but not during the nighttime (active phase feeding; APF). The goal of the present study was to clarify whether the molecular circadian clock is associated with the mechanisms that underly the metabolic disorders in mice brought about by SPF. We compared the effects of dominant negative Clock gene mutation on metabolic disruption and obesity brought about by SPF in mice. The consumption of food during SP increased body weight, adipose tissue mass and lipogenic gene expression in metabolic tissues, as well as hyperinsulinemia, hyperleptinemia and hepatic lipid accumulation in wild-type and Clock mutant mice, and there were no significant differences between genotypes except for the body weight increase which was attenuated by the Clock mutation. Temporal expression of Per2 was synchronized to feeding rhythms in the liver of both genotypes, although the expression of Dbp, a representative clock-controlled gene, was significantly damped in peripheral tissues of Clock mutant mice. These findings suggest that the molecular clock is not essentially associated with metabolic disruption caused by SPF. Desynchronized food consumption and central clock-dependent behaviour as well as rhythmic metabolic mechanisms might be associated with the metabolic disruption caused by SPF.