IntroductionPhospholipids are essential components of cellular membranes and are closely associated with cellular functions, but relationships involving skeletal muscle phospholipid profiles and their physiological phenotypes have remained unclear.MethodsWe carried out comprehensive phospholipid analyses using liquid chromatography–tandem mass spectrometry to determine the phospholipid profiles of skeletal muscles derived from muscle‐wasting mouse models, including denervated and Duchenne muscular dystrophy mouse models (mdx) as well as rescued mdx mice expressing truncated dystrophin.ResultsConsistent phosphatidylcholine and phosphatidylethanolamine alterations in skeletal muscles isolated from denervated and mdx mice were observed. Notably, the levels of these phospholipids binding polyunsaturated fatty acids were reduced in denervated and mdx muscles. Moreover, rescuing the mdx pathology by expressing truncated dystrophin led to the restoration of phospholipid profiles.DiscussionOur findings support the hypothesis that phospholipid profiles of the skeletal muscle may be associated with skeletal muscle function.