| First Author | York B | Year | 2012 |
| Journal | Cell Metab | Volume | 15 |
| Issue | 5 | Pages | 752-63 |
| PubMed ID | 22560224 | Mgi Jnum | J:184779 |
| Mgi Id | MGI:5426310 | Doi | 10.1016/j.cmet.2012.03.020 |
| Citation | York B, et al. (2012) Ablation of steroid receptor coactivator-3 resembles the human CACT metabolic myopathy. Cell Metab 15(5):752-63 |
| abstractText | Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of beta-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic. |
