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

Cell Rep. 2017 Nov 28;21(9):2367-2375. doi: 10.1016/j.celrep.2017.11.004.

Abstract

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.

Keywords: Klf15; Per3; adipocyte precursor cells; adipogenesis; circadian clock.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics
  • Adipogenesis / physiology*
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Kruppel-Like Transcription Factors
  • Mice
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Klf15 protein, mouse
  • Kruppel-Like Transcription Factors
  • Per3 protein, mouse
  • Period Circadian Proteins
  • Transcription Factors