| First Author | Amador A | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 5 | Pages | e0196787 |
| PubMed ID | 29723273 | Mgi Jnum | J:265505 |
| Mgi Id | MGI:6157418 | Doi | 10.1371/journal.pone.0196787 |
| Citation | Amador A, et al. (2018) Distinct roles for REV-ERBalpha and REV-ERBbeta in oxidative capacity and mitochondrial biogenesis in skeletal muscle. PLoS One 13(5):e0196787 |
| abstractText | The nuclear receptors REV-ERBalpha and REV-ERBbeta have been demonstrated to be core members of the circadian clock and participate in the regulation of a diverse set of metabolic functions. Due to their overlapping tissue expression patterns and gene expression profiles, REV-ERBbeta is thought to be redundant to REV-ERBalpha. Recent work has highlighted REV-ERBalpha's role in the regulation of skeletal muscle oxidative capacity and mitochondrial biogenesis. Considering the similarity between the REV-ERBs and the hypothesized overlap in function, we sought to determine whether REV-ERBbeta-deficiency presented with a similar skeletal muscle phenotype as REV-ERBalpha-deficiency. Ectopic overexpression in C2C12 cells demonstrated that REV-ERBbeta drives mitochondrial biogenesis and the expression of genes involved in fatty acid oxidation. Intriguingly, knock down of REV-ERBbeta in C2C12 cultures also resulted in mitochondrial biogenesis and increased expression of genes involved in fatty acid beta-oxidation. To determine whether these effects occurred in vivo, we examined REV-ERBbeta-deficient mice and observed a similar increase in expression of genes involved in mitochondrial biogenesis and fatty acid beta-oxidation. Consistent with these results, REV-ERBbeta-deficient mice exhibited an altered metabolic phenotype compared to wild-type littermate controls when measured by indirect calorimetry. This likely compensated for the increased food consumption that occurred, possibly aiding in the maintenance of their weight over time. Since feeding behaviors are a direct circadian output, this study suggests that REV-ERBbeta may have more subtle effects on circadian behaviors than originally identified. Furthermore, these data implicate REV-ERBbeta in the control of skeletal muscle metabolism and energy expenditure and suggest that development of REV-ERBalpha versus REV-ERBbeta selective ligands may have therapeutic utility in the treatment of metabolic syndrome. |
