Characteristics of Circadian Gene Expressions in Mice White Adipose Tissue and 3T3-L1 Adipocytes

Abstract

Most, if not all, of physiological and behavioral processes exhibit circadian rhythms. Recently, molecular clocks similar to those operating in the suprachiasmatic nucleus (SCN) neurons have been found in several peripheral tissues. Among peripheral tissues, several recent studies have revealed that white adipose tissues secrete a number of biologically active molecules such as leptin, resistin, adiponectin, etc. Importantly, the levels of these cytokine-like molecules are associated with development of lifestyle-related diseases such as diabetic mellitus, cardiovascular diseases, and obesity. In this study, we attempted to characterize circadian gene expression in adipose tissue. Here, we show that the expression of several clock genes exhibits daily oscillation in mice white adipocytes. Circadian expression of adipocytes-related genes such as peroxisome proliferator-activated receptor (PPAR) γ2 was also observed. Interestingly, expression pattern of some clock genes in adipocytes is distinct from that in stromal-vascular fractions containing preadipocytes. In addition to these in vivo studies, we demonstrated that serum- or dexamethasone-shock induced the cyclic gene expression of clock genes in cultured adipocytes. Consequently, we are led to conclude that adipocytes contain the machineries necessary for circadian oscillation similar to that found in SCN. We then examined that whether the pharmacological effects of PPARγ2 ligand depend on the time of administration. Consist with its receptor levels, the pharmacological effects of PPARγ ligand administered during a dark period were more efficient than those during a light period in mice. These results suggest that chronotherapy targeted for adipocyte functions could be effective in improving of the symptoms of hyperlipidemia and other related diseases.