Abstract

Exercise training influences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; however, the molecular mechanism of this influence on compositional changes is poorly understood. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, the fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training induces these adaptations, together with increased PGC-1α, PGC-1α may contribute to the exercise-mediated change in phospholipid fatty acid composition. To determine the role of PGC-1α, we performed lipidomic analyses of skeletal muscle from genetically modified mice that overexpress PGC-1α in skeletal muscle or that carry KO alleles of PGC-1α. We found that PGC-1α affected lipid profiles in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC-1α was required for these alterations. Because phospholipid fatty acid composition influences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle.

Highlights

  • Institutes of Biomedical Innovation, Health, and Nutrition, Ibaraki, Osaka 567-0085, Japan; Department of Cell Biology and Anatomy,††† Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan; and Department of Anatomy,§§§ University of Hong Kong, Pokfulam, Hong Kong

  • To examine the differences between the lipid profiles of glycolytic and oxidative muscle fibers such as extensor digitorum longus (EDL) and soleus, and to determine the impact of PGC-1␣ on these profiles, lipidomic analyses were performed using highresolution LC/MS that allows for accurate identification of lipid species

  • It has been reported that exercise training modifies phospholipid species in the skeletal muscles [4,5,6,7,8,9,10,11]; the molecular mechanisms involved in these modifications

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Summary

Introduction

Exercise training influences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; the molecular mechanism of this influence on compositional changes is poorly understood. Because exercise training induces these adaptations, together with increased PGC-1␣, PGC-1␣ may contribute to the exercise-mediated change in phospholipid fatty acid composition. We found that PGC-1␣ affected lipid profiles in skeletal muscle and increased several phospholipid species in glycolytic muscle, namely phosphatidylcholine (PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We found that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic muscle and that PGC-1␣ was required for these alterations. Because phospholipid fatty acid composition influences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle.—Senoo, N., N. PGC-1␣-mediated changes in phospholipid profiles of exercise-trained skeletal muscle.

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