The Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15

Summary The generation of new adipocytes from precursor cells (adipogenesis) has implications for systemic metabolism and is a commonly used model for studying the process of cell differentiation in vitro . Previous studies from us and others suggested that the peripheral circadian clock can influence adipogenesis in vitro , but the mechanisms driving this activity and the relevance for adipogenesis in vivo are unknown. Here we reveal that mouse adipocyte precursor cells (APCs) contain a circadian clock that oscillates in vivo . We expose context-specific features of the clock in APCs: expression of the canonical core clock component Per1 does not significantly oscillate, whereas the lesser-understood paralog Per3 has a prominent rhythm. We discovered that deletion of Per3 promotes adipogenesis in vivo by a clock output pathway in which PER3 and BMAL1 directly regulate Klf15 expression. These findings demonstrate that Per3 has a major role in the APC clock and regulates adipogenesis in vivo .