Sarcolipin: A Key Thermogenic and Metabolic Regulator in Skeletal Muscle

Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis and heat production, and contributes to temperature homeostasis. SLN also affects whole-body metabolism and weight gain in mice, and is upregulated in various muscle diseases including muscular dystrophy, suggesting a role for SLN during increased metabolic demand. In this review we also highlight the physiological roles of skeletal muscle beyond contraction.