Journal article
Adipocyte NR1D1 dictates adipose tissue expansion during obesity
- Abstract:
- 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 (Nr1d1Flox2-6:AdipoqCre), 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, Nr1d1Flox2-6:AdipoqCre 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.7554/elife.63324
Authors
- Publisher:
- eLife Sciences Publications
- Journal:
- eLife More from this journal
- Volume:
- 10
- Article number:
- e63324
- Publication date:
- 2021-08-05
- Acceptance date:
- 2021-07-30
- DOI:
- EISSN:
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2050-084X
- Pmid:
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34350828
- Language:
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English
- Keywords:
- Pubs id:
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1190497
- Local pid:
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pubs:1190497
- Deposit date:
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2021-09-16
- ARK identifier:
Terms of use
- Copyright holder:
- Hunter et al.
- Copyright date:
- 2021
- Rights statement:
- © 2021, Hunter et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
- Licence:
- CC Attribution (CC BY)
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