| First Author | Coste A | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 44 | Pages | 17187-92 |
| PubMed ID | 18957541 | Mgi Jnum | J:144060 |
| Mgi Id | MGI:3829839 | Doi | 10.1073/pnas.0808207105 |
| Citation | Coste A, et al. (2008) The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}. Proc Natl Acad Sci U S A 105(44):17187-92 |
| abstractText | Transcriptional control of metabolic circuits requires coordination between specific transcription factors and coregulators and is often deregulated in metabolic diseases. We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial function and in energy expenditure as a consequence of activation of PGC-1alpha. By controlling the expression of the only characterized PGC-1alpha acetyltransferase GCN5, SRC-3 induces PGC-1alpha acetylation and consequently inhibits its activity. Interestingly, SRC-3 expression is induced by caloric excess, resulting in the inhibition of PGC-1alpha activity and energy expenditure, whereas caloric restriction reduces SRC-3 levels leading to enhanced PGC-1alpha activity and energy expenditure. Collectively, these data suggest that SRC-3 is a critical link in a cofactor network that uses PGC-1alpha as an effector to control mitochondrial function and energy homeostasis. |
