Retinoid acid-related orphan receptor γ, RORγ, participates in diurnal transcriptional regulation of lipid metabolic genes

摘要: The hepatic circadian clock plays a pivotal role in regulating major aspects of energy homeostasis and lipid metabolism. In this study, we show that RORγ robustly regulates the rhythmic expression several metabolic genes, including insulin-induced gene 2a, Insig2a, elongation very long chain fatty acids-like 3, Elovl3 sterol 12α-hydroxylase, Cyp8b1, by enhancing their at ZT20-4. time-dependent increase correlates with pattern RORγ. enhanced recruitment to ROREs promoter region, increased histone acetylation, reporter mutation analysis support concept transcription genes directly binding regulatory region. Consistent disrupted number loss reduced level lipids liver blood ZT-preferred manner. Particularly whole-body bile acid pool size was considerably RORγ−/− mice part through its regulation Cyp genes. Similar observations were made liver-specific RORγ-deficient mice. Altogether, our study indicates functions as an important link between transcriptional