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The nuclear receptor ERRα is essential for skeletal muscle metabolic adaptations to endurance training (1164.2)
Author(s) -
LaBarge Samuel,
McDonald Marisa,
Hamilton Angelica,
Turcotte Lorraine,
Huss Janice
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1164.2
Subject(s) - mitochondrial biogenesis , citrate synthase , endocrinology , medicine , ampk , skeletal muscle , endurance training , chemistry , downregulation and upregulation , receptor , mitochondrion , biochemistry , gene , protein kinase a , phosphorylation , enzyme
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 RTE blood lactate was elevated in trained M‐ERRα‐/‐ mice (>12mmol/L), similar to sedentary mice, suggesting the training effects on muscle aerobic capacity was blunted. Consistently, succinate dehydrogenase and CS activities were increased in trained WT but not M‐ERRα‐/‐ muscles. Our data suggest that ERRα is involved in AMPK‐mediated skeletal muscle metabolic adaptation following exercise training…