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Muscle mTORC1 can be activated by feeding and contraction. Here, muscle mTORC1 signaling, protein synthesis, mass, and function are characterized in a genetic mouse model that separates these 2 major modes of muscle mTORC1 regulation. AKT signaling is required for feeding-induced muscle mTORC1 signaling and protein synthesis, and mice expressing a mutant of tuberous sclerosis complex 2 (TSC2) that cannot be phosphorylated by AKT specifically in skeletal muscle (SkM-TSC2-5A) attenuate these effects of feeding. Despite this loss of postprandial protein synthesis, SkM-TSC2-5A mice have similar muscle and myofiber size compared with SkM-TSC2-WT mice. SkM-TSC2-5A mice maintain normal muscle mTORC1 activation in response to contraction and exhibit no differences in atrophy-related gene expression or ribosomal content. SkM-TSC2-5A mice exhibit improved maximal endurance capacity without changes in muscle contractile function. This phenotype occurs without alterations in muscle glycogen content or myofiber type, but it does coincide with a modest increase in muscle mitochondrial content. Therefore, AKT-mediated phosphorylation of TSC2 is required for postprandial mTORC1 activation and the induction of protein synthesis; however, these are dispensable for the development and maintenance of muscle mass in sedentary mice.<\/jats:p>","DOI":"10.1172\/jci.insight.210523","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:00:16Z","timestamp":1789056016000},"source":"Crossref","is-referenced-by-count":0,"title":["Feeding-induced muscle mTORC1 signaling regulates postprandial protein synthesis and endurance but not muscle size"],"prefix":"10.1172","volume":"11","author":[{"given":"Samuel C.","family":"Lapp","sequence":"first","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. 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