| First Author | Ma D | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 50 | Pages | 39087-95 |
| PubMed ID | 20947495 | Mgi Jnum | J:167589 |
| Mgi Id | MGI:4868572 | Doi | 10.1074/jbc.M110.151688 |
| Citation | Ma D, et al. (2010) Neuronal inactivation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) protects mice from diet-induced obesity and leads to degenerative lesions. J Biol Chem 285(50):39087-95 |
| abstractText | Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a transcriptional coactivator that regulates diverse aspects of energy metabolism in peripheral tissues. Mice deficient in PGC-1alpha have elevated metabolic rate and are resistant to diet-induced obesity. However, it remains unknown whether this alteration in energy balance is due to the action of PGC-1alpha in peripheral tissues or the central nervous system. In this study, we generated neuronal PGC-1alpha knock-out mice (BalphaKO) using calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha)-Cre to address its role in the regulation of energy balance and neuronal function. Unlike whole body PGC-1alpha null mice, BalphaKO mice have normal adaptive metabolic response to starvation and cold exposure in peripheral tissues. In contrast, BalphaKO mice are hypermetabolic, and similar to whole body PGC-1alpha null mice, are also resistant to diet-induced obesity, resulting in significantly improved metabolic profiles. Neuronal inactivation of PGC-1alpha leads to striatal lesions that are reminiscent of neurodegeneration in whole body PGC-1alpha null brain and impairs nutritional regulation of hypothalamic expression of genes that regulate systemic energy balance. Together, these studies have demonstrated a physiological role for neuronal PGC-1alpha in the control of energy balance. Our results also implicate CaMKIIalpha-positive neurons as an important part of the neural circuitry that governs energy expenditure in vivo. |
