Adipocyte NR1D1 dictates adipose tissue expansion during obesity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34350828.
- Also identified by DOI 10.7554/eLife.63324 and PMC identifier 8360653.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global <i>Nr1d1</i> deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (<i>Nr1d1<sup>Flox2-6</sup>:Adipoq<sup>Cre</sup></i>), 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, <i>Nr1d1<sup>Flox2-6</sup>:Adipoq<sup>Cre</sup></i> 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.
Medical subject headings
- Adipocytes
- Adipose Tissue
- Nuclear Receptor Subfamily 1, Group D, Member 1
- Obesity