Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats

Highlights•Eicosapentaenoic acid (EPA) possesses high PPARδ-agonist activity•EPA intake increases proportion of slow-twitch type 1 muscle fibers•EPA intake promotes oxidative metabolism and improves muscle function•EPA activates both PPARδ and AMPK pathwaysSummaryMuscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance.