| First Author | Leone TC | Year | 2005 |
| Journal | PLoS Biol | Volume | 3 |
| Issue | 4 | Pages | e101 |
| PubMed ID | 15760270 | Mgi Jnum | J:96306 |
| Mgi Id | MGI:3529932 | Doi | 10.1371/journal.pbio.0030101 |
| Citation | Leone TC, et al. (2005) PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis. PLoS Biol 3(4):e101 |
| abstractText | The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/-) mice. With age, the PGC-1alpha(-/-) mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/-) mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/-) mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/-) mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/-) mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/-) mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/-) mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life. |
