The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (Nr1d1 Flox2-6:Adipoq Cre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Nr1d1 Flox2-6:Adipoq Cre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.

Original languageEnglish
Article numbere63324
Early online date5 Aug 2021
Publication statusPublished - 12 Aug 2021


  • Adipocytes/metabolism
  • Adipose Tissue/metabolism
  • Animals
  • Energy Metabolism
  • Gene Deletion
  • Lipid Metabolism
  • Male
  • Mice
  • Nuclear Receptor Subfamily 1, Group D, Member 1/genetics
  • Obesity/genetics


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