Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle.
Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle.
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DOI：
10.1371/journal.pone.0196787
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Solt LA
中科院分区：
文献类型：
--
作者：
Amador A;Campbell S;Kazantzis M;Lan G;Burris TP;Solt LA
The nuclear receptors REV-ERBα and REV-ERBβ 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-ERBβ is thought to be redundant to REV-ERBα. Recent work has highlighted REV-ERBα’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-ERBβ-deficiency presented with a similar skeletal muscle phenotype as REV-ERBα-deficiency. Ectopic overexpression in C2C12 cells demonstrated that REV-ERBβ drives mitochondrial biogenesis and the expression of genes involved in fatty acid oxidation. Intriguingly, knock down of REV-ERBβ in C2C12 cultures also resulted in mitochondrial biogenesis and increased expression of genes involved in fatty acid β-oxidation. To determine whether these effects occurred in vivo, we examined REV-ERBβ-deficient mice and observed a similar increase in expression of genes involved in mitochondrial biogenesis and fatty acid β-oxidation. Consistent with these results, REV-ERBβ-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-ERBβ may have more subtle effects on circadian behaviors than originally identified. Furthermore, these data implicate REV-ERBβ in the control of skeletal muscle metabolism and energy expenditure and suggest that development of REV-ERBα versus REV-ERBβ selective ligands may have therapeutic utility in the treatment of metabolic syndrome.
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影响因子：
--
作者：
Marcheva, Biliana;Ramsey, Kathryn M;Peek, Clara B;Affinati, Alison;Maury, Eleonore;Bass, Joseph
通讯作者：
Bass, Joseph
影响因子：
8
作者：
De Mei C;Ercolani L;Parodi C;Veronesi M;Lo Vecchio C;Bottegoni G;Torrente E;Scarpelli R;Marotta R;Ruffili R;Mattioli M;Reggiani A;Wade M;Grimaldi B
通讯作者：
Grimaldi B
影响因子：
16.6
作者：
Banerjee, Subhashis;Wang, Yongjun;Burris, Thomas P.
通讯作者：
Burris, Thomas P.
影响因子：
--
作者：
FORMAN, BM;CHEN, J;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
3.7
作者：
Crumbley C;Burris TP
通讯作者：
Burris TP