The circadian clock machinery controls adiponectin expression

Adiponectin, an adipokine involved in glucose and lipid metabolism, exhibits a circadian manner of expression. Adiponectin expression is mediated by the helix-loop-helix transcription factor sterol regulatory element binding protein (SREBP)-1c. In this study, we tested whether the circadian clock helix-loop-helix transcription factors CLOCK and BMAL1 regulate adiponectin expression. We found that adiponectin expression is regulated by the clock through the circadian expression of its transcription factor peroxisome proliferator-activated receptor γ (PPARγ) and its co-activator PPARγ co-activator 1α (PGC1α) in mouse white adipose tissue and differentiated adipocytes. In addition, reconstitution of the core clock mechanism and siRNA experiments in cell culture suggest that the clock directly activates the adiponectin promoter and mediates its expression. In summary, adiponectin expression is regulated by the circadian clock and through the circadian expression of its transcription factor PPARγ and its co-activator PGC1α.