This article is available online at http://www.jlr.org infl uences cell permeability and receptor stability at the cell membrane, these phospholipids may contribute to exercise training-mediated functional changes in the skeletal muscle. Phospholipids are important structural components of membranes, and they infl uence a number of physical properties related to membrane function, including fl uidity, permeability, and the anchoring of membrane-related proteins. Because altering dietary fatty acids ( 1-3 ) and Abstract Exercise training infl uences phospholipid fatty acid composition in skeletal muscle and these changes are associated with physiological phenotypes; however, the molecular mechanism of this infl uence on compositional changes is poorly understood. Peroxisome proliferator-activated receptor ␥ coactivator 1 ␣ (PGC-1 ␣ ), a nuclear receptor coactivator, promotes mitochondrial biogenesis, the fi ber-type switch to oxidative fi bers, and angiogenesis in skeletal muscle. 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. To determine the role of PGC-1 ␣ , we performed lipidomic analyses of skeletal muscle from genetically modified mice that overexpress PGC-1 ␣ in skeletal muscle or that carry KO alleles of PGC-1 ␣ . We found that PGC-1 ␣ affected lipid profi les 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-1 ␣ was required for these alterations. Because phospholipid fatty acid composition