Figure 5.

GCN5 regulates mitochondrial and fatty acid metabolism in skeletal muscle cells. (A) GCN5 downregulates PGC-1α-induced mitochondrial gene expression. C₂C₁₂ myotubes were infected for 3 days with the indicated adenoviruses. Total RNA was extracted and analyzed for mitochondrial, fatty acid utilization and transcriptional regulator gene expression using quantitative RT–PCR analysis. (B) Nicotinamide downregulates PGC-1α-induced mitochondrial and fatty acid oxidation gene expression in C₂C₁₂ myotubes and (C) MEFs. C₂C₁₂ cells were infected with the indicated adenoviruses. At day 3 after infection, cells were treated for 12 h with 10 mM nicotinamide. Confluent MEFs were also treated for 12 h with nicotinamide and harvested for RNA analysis. (D) GCN5 and nicotinamide prevented PGC-1α-increased fatty acid oxidation rates. Cells were treated as in (A–C), but oleic acid oxidation assays were performed as described in Materials and methods. Values represent the mean of 2–3 experiments performed in duplicate. Error bars represent s.e.m. Statistical analyses were performed using Student's t-test. ^*P<0.05 and ^**P<0.005.