Adipocyte NR1D1 dictates adipose tissue expansion during obesity
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:...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63324 |
| _version_ | 1811253336002789376 |
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| author | Ann Louise Hunter Charlotte E Pelekanou Nichola J Barron Rebecca C Northeast Magdalena Grudzien Antony D Adamson Polly Downton Thomas Cornfield Peter S Cunningham Jean-Noel Billaud Leanne Hodson Andrew SI Loudon Richard D Unwin Mudassar Iqbal David W Ray David A Bechtold |
| author_facet | Ann Louise Hunter Charlotte E Pelekanou Nichola J Barron Rebecca C Northeast Magdalena Grudzien Antony D Adamson Polly Downton Thomas Cornfield Peter S Cunningham Jean-Noel Billaud Leanne Hodson Andrew SI Loudon Richard D Unwin Mudassar Iqbal David W Ray David A Bechtold |
| author_sort | Ann Louise Hunter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:49:20Z |
| format | Article |
| id | doaj.art-ea65ba8216cf4fc8be509f4be399aaf8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:49:20Z |
| publishDate | 2021-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ea65ba8216cf4fc8be509f4be399aaf82022-12-22T03:24:27ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.63324Adipocyte NR1D1 dictates adipose tissue expansion during obesityAnn Louise Hunter0https://orcid.org/0000-0002-3874-4852Charlotte E Pelekanou1Nichola J Barron2Rebecca C Northeast3https://orcid.org/0000-0002-3121-2802Magdalena Grudzien4Antony D Adamson5Polly Downton6https://orcid.org/0000-0002-1617-6153Thomas Cornfield7Peter S Cunningham8Jean-Noel Billaud9Leanne Hodson10Andrew SI Loudon11Richard D Unwin12Mudassar Iqbal13David W Ray14David A Bechtold15https://orcid.org/0000-0001-8676-8704Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomDigital Insights, Qiagen, Redwood City, United StatesOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomStoller Biomarker Discovery Centre, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomDivision of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United KingdomCentre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomThe 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.https://elifesciences.org/articles/63324circadian clockenergy metabolismobesityadiposeRev-erb-alphaRev-erbα |
| spellingShingle | Ann Louise Hunter Charlotte E Pelekanou Nichola J Barron Rebecca C Northeast Magdalena Grudzien Antony D Adamson Polly Downton Thomas Cornfield Peter S Cunningham Jean-Noel Billaud Leanne Hodson Andrew SI Loudon Richard D Unwin Mudassar Iqbal David W Ray David A Bechtold Adipocyte NR1D1 dictates adipose tissue expansion during obesity eLife circadian clock energy metabolism obesity adipose Rev-erb-alpha Rev-erbα |
| title | Adipocyte NR1D1 dictates adipose tissue expansion during obesity |
| title_full | Adipocyte NR1D1 dictates adipose tissue expansion during obesity |
| title_fullStr | Adipocyte NR1D1 dictates adipose tissue expansion during obesity |
| title_full_unstemmed | Adipocyte NR1D1 dictates adipose tissue expansion during obesity |
| title_short | Adipocyte NR1D1 dictates adipose tissue expansion during obesity |
| title_sort | adipocyte nr1d1 dictates adipose tissue expansion during obesity |
| topic | circadian clock energy metabolism obesity adipose Rev-erb-alpha Rev-erbα |
| url | https://elifesciences.org/articles/63324 |
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