transcriptomic study showing effect of exercise and PPARd activation in mouse skeletal muscle. Mus musculus

We report the identification of muscle Pparδ as a key regulator of adaptive energy metabolism. Its knockout in skeletal muscle completely abolishes the exercise-induced metabolic shift in energy substrate utilization. When activated by a selective ligand GW501516, Pparδ induces exercise-mimicking effects including elevated energy expenditure, a shift in energy substrate utilization, reduced diet-induced obesity, and enhanced endurance performance without muscle fiber-type transformation or mitochondrial proliferation. These effects appear to be dependent on muscle Pparδ and are not induced by GW501516 in mice with muscle-specific Pparδ deletion. RNA-seq analyses identify a unique Pparδ-controlled gene network in skeletal muscle that mediates ligand-induced energy expenditure and substrate utilization.