| First Author | Delezie J | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 8 | Pages | 3321-35 |
| PubMed ID | 22562834 | Mgi Jnum | J:187464 |
| Mgi Id | MGI:5437166 | Doi | 10.1096/fj.12-208751 |
| Citation | Delezie J, et al. (2012) The nuclear receptor REV-ERBalpha is required for the daily balance of carbohydrate and lipid metabolism. FASEB J 26(8):3321-35 |
| abstractText | Mutations of clock genes can lead to diabetes and obesity. REV-ERBalpha, a nuclear receptor involved in the circadian clockwork, has been shown to control lipid metabolism. To gain insight into the role of REV-ERBalpha in energy homeostasis in vivo, we explored daily metabolism of carbohydrates and lipids in chow-fed, unfed, or high-fat-fed Rev-erbalpha(-/-) mice and their wild-type littermates. Chow-fed Rev-erbalpha(-/-) mice displayed increased adiposity (2.5-fold) and mild hyperglycemia ( approximately 10%) without insulin resistance. Indirect calorimetry indicates that chow-fed Rev-erbalpha(-/-) mice utilize more fatty acids during daytime. A 24-h nonfeeding period in Rev-erbalpha(-/-) animals favors further fatty acid mobilization at the expense of glycogen utilization and gluconeogenesis, without triggering hypoglycemia and hypothermia. High-fat feeding in Rev-erbalpha(-/-) mice 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 ( approximately 2-fold) in muscle and adipose tissue of Rev-erbalpha(-/-) mice. We show that CLOCK, up-regulated (2-fold) at night in Rev-erbalpha(-/-) 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. |
