Research ReportInfluence of the core circadian gene “Clock” on obesity and leptin resistance in mice

Alterations in metabolism could be due to cell-autonomous effects associated with altered expression of Clock in central nervous system feeding centers and/or peripheral tissues involved in metabolism. Clock mutant mice are hyperphagic and obese, which indicates that Clock is related to obesity. In the present study, we used intracerebroventricular injection of recombinant adenoviral vector harboring Clock genes to explore the role of Clock on diet induced obesity and the mechanisms involved in leptin resistance and leptin signaling in mice. The results demonstrated that expression of Clock in the arcuate nucleus of diet induced obesity mice was down-regulated. The recombinant adenoviral vector harboring Clock genes could reduce obesity indexes of diet induced obesity mice including body weight, BMI and total fat mass, attenuate hyperleptinemia, increase leptin sensitivity and decrease accumulated suppressor of cytokine signaling-3 in the arcuate nucleus. These results indicate that Clock plays an important role on obesity, which may be involved in leptin resistance and regulation of suppressor of cytokine signaling-3 in arcuate nucleus.

► ICV injection of RAV-C can reduce body weight, BMI and total fat mass of DIO mice. ► ICV injection of RAV-C can increase leptin sensitivity of DIO mice. ► ICV injection of RAV-C can decrease accumulated SOCS3 of DIO mice. ► Clock may be involved in regulation of leptin resistant and SOCS3 in ARC.