Adipocyte NR1D1 dictates adipose tissue expansion during obesity

• Published in: eLife Vol. 10
• Main Authors: Hunter, Ann Louise, Pelekanou, Charlotte E, Barron, Nichola J, Northeast, Rebecca C, Grudzien, Magdalena, Adamson, Antony D, Downton, Polly, Cornfield, Thomas, Cunningham, Peter S, Billaud, Jean-Noel, Hodson, Leanne, Loudon, Andrew Si, Unwin, Richard D, Iqbal, Mudassar, Ray, David W, Bechtold, David A
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 05.08.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adipocytes; Adipocytes - metabolism; adipose; Adipose tissue; Adipose Tissue - metabolism; Adipose tissues; Animals; Biotechnology industry; Body fat; Body temperature; Cell Biology; circadian clock; Circadian rhythm; Circadian rhythms; Collagen; Energy; Energy Metabolism; Fatty acids; Fibrosis; Food; Gene Deletion; Gene expression; High fat diet; Insulin; Insulin resistance; Lipid Metabolism; Lipids; Lipogenesis; Liu, Timothy; Male; Medicine; Metabolism; Mice; Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics; Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism; Obesity; Obesity - genetics; Obesity - metabolism; Phenotypes; Physiological aspects; Physiology; Proteins; Rev-erb-alpha; Rev-erbα; Transcription; United States; Rev-erb-alpha; mouse; cell biology; adipose; medicine; Rev-erbα; circadian clock; energy metabolism; obesity
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.63324

The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion ( ), 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, 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.