Kojima_2026_PLoS.One_21_e0348366

Alaska pollock protein (APP) promotes skeletal muscle hypertrophy, particularly in fast-twitch fibers. Using a time-controlled feeding model, plasma collected 90 min after APP intake markedly enhanced C2C12 myotube hypertrophy and contractility. At this time point, plasma glucagon-like peptide-1 levels were significantly elevated, suggesting the involvement of circulating factors associated with APP intake. Proteomic and lipidomic analyses of skeletal muscle identified 2302 proteins and 538 lipids, and revealed pronounced remodeling of lipid metabolism, including a 127% increase in docosahexaenoic acid (DHA)-containing phospholipids in hypertrophied fast-twitch fibers, partially resembling endurance training adaptations. APP also upregulated adipose triglyceride lipase and hormone-sensitive lipase in the skeletal muscle, indicating enhanced lipid catabolism. Although APP contained only trace amounts of DHA (~0.008% of the diet), this level was substantially lower than the dietary DHA level previously reported to alter tissue lipid composition. Therefore, APP-derived DHA was unlikely to be the primary driver of the observed phenotype. Together, these findings indicate that APP functions primarily as a high-quality protein source that promotes muscle anabolic responses and is associated with remodeling of lipid metabolic pathways, thereby potentially contributing to a circulating environment favorable for skeletal muscle hypertrophy and metabolic regulation.