| First Author | Summermatter S | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 408 |
| Issue | 1 | Pages | 180-5 |
| PubMed ID | 21501593 | Mgi Jnum | J:172051 |
| Mgi Id | MGI:5003372 | Doi | 10.1016/j.bbrc.2011.04.012 |
| Citation | Summermatter S, et al. (2011) Coordinated balancing of muscle oxidative metabolism through PGC-1alpha increases metabolic flexibility and preserves insulin sensitivity. Biochem Biophys Res Commun 408(1):180-5 |
| abstractText | The peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1alpha on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1alpha in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1alpha induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1alpha enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1alpha boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1alpha coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1alpha does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1alpha mimic the beneficial effects of endurance training on muscle metabolism in this context. |
