Adipocyte NR1D1 dictates adipose tissue expansion during obesity

被引：35

作者：

Hunter, Ann Louise ^{[1
]}

Pelekanou, Charlotte E. ^{[1
]}

Barron, Nichola J. ^{[1
]}

Northeast, Rebecca C. ^{[1
]}

Grudzien, Magdalena ^{[1
]}

Adamson, Antony D. ^{[1
]}

Downton, Polly ^{[1
]}

Cornfield, Thomas ^{[2
,3
]}

Cunningham, Peter S. ^{[1
]}

Billaud, Jean-Noel ^{[4
]}

Hodson, Leanne ^{[2
,3
]}

Loudon, Andrew S., I ^{[1
]}

Unwin, Richard D. ^{[5
]}

Iqbal, Mudassar ^{[6
]}

Ray, David W. ^{[2
,3
]}

Bechtold, David A. ^{[1
]}

机构：

[1] Univ Manchester, Fac Biol Med & Hlth, Ctr Biol Timing, Manchester, Lancs, England

[2] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[3] John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford, England

[4] Qiagen, Digital Insights, Redwood City, CA USA

[5] Univ Manchester, Fac Biol Med & Hlth, Stoller Biomarker Discovery Ctr, Div Canc Sci, Manchester, Lancs, England

[6] Univ Manchester, Fac Biol Med & Hlth, Div Informat Imaging & Data Sci, Manchester, Lancs, England

来源：

ELIFE | 2021年 / 10卷

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

REV-ERB-ALPHA; CIRCADIAN CLOCK; METABOLISM; TRANSCRIPTION; LIVER; RHYTHMS; GENE; COORDINATION; EXPRESSION; BEHAVIOR;

D O I：

10.7554/eLife.63324

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The circadian clock component NR1D1 (REVERB alpha) 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.

引用

页数：26

共 76 条

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