The nuclear receptor REV-ERBα is required for the daily balance of carbohydrate and lipid metabolism
Abstract
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-erbα(-/-) 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 (∼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.
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Rev-erbα−/− mice seem to favor fatty acid oxidation at the expense of glycogen utilization.
“Rev-erbα−/− mice seem to favor fatty acid oxidation at the expense of glycogen utilization [29].”
From Circadian control of glucose metabolism (2014) · cites this paper as [29]
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- Authors
- Delezie, J., Dumont, S., Dardente, H., Oudart, H., Gréchez‐Cassiau, A., Klosen, P., Teboul, M., Delaunay, F., Pévet, P., & Challet, E.
- Affiliations
- Institut des Neurosciences Cellulaires et Intégratives (FR)
- Université de Tours (FR)
- Institut Pluridisciplinaire Hubert Curien (FR)
- Institut de Biologie Valrose (FR)
- Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences University of Strasbourg Strasbourg France
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-05-04
- Volume
- 26
- Issue
- 8
- Pages
- 3321-3335
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2128073839
- Cited by
- 252
- References
- 63
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 20 · 2023: 15 · 2022: 23 · 2021: 14 · 2020: 29 · 2019: 18 · 2018: 16 · 2017: 18 · 2016: 22 · 2015: 18 · 2014: 15 · 2013: 14 · 2012: 5
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Université de Strasbourg
- College of Natural Resources and Sciences, Humboldt State University
- European Commission (CRESCENDO LSHM-CT-2005-018652)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- NR1D1, circadian clock, carbohydrate metabolism, lipid metabolism, energy homeostasis, adiposity, hyperglycemia, lipoprotein lipase, clock genes, fatty acid utilization, gluconeogenesis, high-fat diet, metabolic syndrome, circadian rhythm disruption
- MeSH terms
- Animals, Circadian Rhythm, Energy Metabolism, Female, Gluconeogenesis, Homeostasis, Insulin Resistance, Lipoprotein Lipase, Liver Glycogen, Male, Motor Activity, Carbohydrate Metabolism, Lipid Metabolism, Mice, CLOCK Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1, Diet, High-Fat
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