The nuclear receptor ERRα is essential for skeletal muscle metabolic adaptations to endurance training (1164.2)

The aim of the present study is to test the hypothesis that the Estrogen-related Receptor α (ERRα) is essential for exercise-mediated metabolic adaptations and that AMPK activates the ERRα pathway. Muscle-specific ERRα-/- (M-ERRα-/-) and M-ERRαWT (WT) mice were subjected to 8wks of treadmill training or 1wk daily AICAR administration. In M-ERRα-/- skeletal muscle citrate synthase (CS) activity was lower ~30% and mitochondrial density was reduced compared to WT. Basal expression of transcripts involved in electron transport (ETC) and β-oxidation were reduced by 25-60%. AICAR treatment induced ERRα and β-oxidation gene expression in WT mice. Exercise training upregulated transcripts involved in mitochondrial biogenesis and ETC, including mitochondrial transcription factor A and cytochrome c, in WT mice. No induction was seen in M-ERRα-/- mice. In run-to-exhaustion (RTE) trials trained WT mice had a greater increase in running distance than M-ERRα-/- mice (+250% vs +50%) relative to sedentary groups. After R...