PPARδ regulates satellite cell proliferation and skeletal muscle regeneration

Skeletal muscle is the most abundant tissue in mammals, making up 45% to 55% of total body mass in humans, and plays important roles in body movement and metabolic regulation. Muscle is made up of different fiber types which have different metabolic requirements that affect the whole body energy homeostasis of the animal [1]. Type 1 fibers are classified as slow fibers and use oxidative metabolism as a fuel source, making them highly fatigue-resistant. Conversely, type 2 fibers are classified as fast fibers, use mainly glycolytic metabolism and are less resistant to fatigue. Type 2 fibers are further broken down into three subtypes, known as types 2a, 2x and 2b, that express corresponding myosin heavy chain (MyHC) isoforms and have decreasing resistance to fatigue. Notably, skeletal muscles are plastic, and fiber-type switching occurs in response to changes in activity and other physiological signaling pathways [2-4]. In addition, skeletal muscle mass is always in a state of hypertrophy or wasting, based on relative use or disuse, respectively [5,6]. Skeletal muscle has superior capacity to regenerate itself upon injury [7].Skeletal muscle plasticity is mainly maintained by a subset of cells known as satellite cells [8,9]. These cells, located beneath the basal lamina of the muscle fiber, are normally maintained in a quiescent state. Satellite cells become activated when the muscle becomes damaged through injury or normal activity. Once activated the cells will reenter the cell cycle and undergo a few rounds of division, then differentiate and fuse with existing muscle fibers to rebuild the damaged area. Satellite cells in the quiescent state express paired-box transcription factor 7 (Pax7) [10]. After activation the cells will express Pax7 and myogenic differentiation antigen 1 (MyoD) concurrently while the cells undergo a few rounds of division (proliferation). These proliferating cells eventually withdraw from the cell cycle and either return to quiescence (self-