The nuclear receptor REV-ERBα is required for the daily balance of carbohydrate and lipid metabolism
FASEB Journal, ISSN: 0892-6638, Vol: 26, Issue: 8, Page: 3321-3335
2012
- 181Citations
- 176Captures
- 3Mentions
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Metrics Details
- Citations181
- Citation Indexes181
- 181
- CrossRef140
- Captures176
- Readers176
- 176
- Mentions3
- References3
- Wikipedia3
Article Description
Mutations of clock genes can lead to diabetes and obesity. REV-ERBα, a nuclear receptor involved in the circadian clockwork, has been shown to control lipid metabolism. To gain insight into the role of REV-ERBα in energy homeostasis in vivo, we explored daily metabolism of carbohydrates and lipids in chow-fed, unfed, or high-fat-fed Rev-erbα mice and their wild-type littermates. Chow-fed Rev-erbα mice displayed increased adiposity (2.5-fold) and mild hyperglycemia (∼10%) without insulin resistance. Indirect calorimetry indicates that chow-fed Rev-erbα mice utilize more fatty acids during daytime. A 24-h nonfeeding period in Rev-erbα animals favors further fatty acid mobilization at the expense of glycogen utilization and gluconeogenesis, without triggering hypoglycemia and hypothermia. High-fat feeding in Rev-erbαmice amplified metabolic disturbances, including expression of lipogenic factors. Lipoprotein lipase (Lpl) gene, critical in lipid utilization/storage, is triggered in liver at night and constitutively up-regulated (∼2-fold) in muscle and adipose tissue of Rev-erbα mice. We show that CLOCK, up-regulated (2-fold) at night in Rev-erbα mice, can transactivate Lpl. Thus, overexpression of Lpl facilitates muscle fatty acid utilization and contributes to fat overload. This study demonstrates the importance of clock-driven Lpl expression in energy balance and highlights circadian disruption as a potential cause for the metabolic syndrome. © FASEB.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84864755952&origin=inward; http://dx.doi.org/10.1096/fj.12-208751; http://www.ncbi.nlm.nih.gov/pubmed/22562834; https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.12-208751; http://www.fasebj.org/cgi/doi/10.1096/fj.12-208751; http://www.fasebj.org/content/26/8/3321
Wiley
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