Skeletal Muscle Thermogenesis and Its Role in Whole Body Energy Metabolism

Abstract

Obesity and diabetes has become a major epidemic across the globe. Controlling obesity has been a challenge since this would require either increased physical activity or reduced caloric intake; both are difficult to enforce. There has been renewed interest in exploiting pathways such as uncoupling protein 1 (UCP1)-mediated uncoupling in brown adipose tissue (BAT) and white adipose tissue to increase energy expenditure to control weight gain. However, relying on UCP1-based thermogenesis alone may not be sufficient to control obesity in humans. On the other hand, skeletal muscle is the largest organ and a major contributor to basal metabolic rate and increasing energy expenditure in muscle through nonshivering thermogenic mechanisms, which can substantially affect whole body metabolism and weight gain. In this review we will describe the role of Sarcolipin-mediated uncoupling of Sarcoplasmic Reticulum Calcium ATPase (SERCA) as a potential mechanism for increased energy expenditure both during cold and diet-induced thermogenesis.

Sex‐specific alterations in whole body energetics and voluntary activity in heterozygous R163C malignant hyperthermia‐susceptible mice

“…Maintenance of a Ca 2+ gradient between the SR lumen and cytoplasm in skeletal muscle is achieved through the coordinated function of the sarcoplasmic reticulum calcium ATPase (SERCA) and ryanodine receptor Ca 2+ channel (RYR1). Inherent changes in the efficiency of calcium cycling across the SR due to RYR1‐mediated Ca 2+ leak is likely to elicit global influences on muscle cell Ca 2+ dynamics across the myoplasm and other organelles, in particular mitochondria, and contribute to myopathic changes 4,22 . Skeletal muscle expressing RYR1 mutations that confer MH susceptibility have also been shown to have chronically elevated cytoplasmic Ca 2+ at rest, increased RYR1‐mediated Ca 2+ leak, depleted SR stores, and abnormal plasmalemmal Ca 2+ fluxes 23 .…”

“…Malignant hyperthermia (MH) is a life‐threatening disorder of skeletal muscle homeostasis that was first described in a family that experienced 10 deaths attributable to anesthesia 1 . A fulminant MH syndrome is characterized by an uncontrolled increase in myoplasmic free calcium (Ca 2+ ) that leads to increased metabolic rate and subsequently results in hyperthermia and muscle rigidity 2‐4 . This energetic crisis can be triggered by volatile anesthetics, depolarizing muscle relaxants (eg, succinylcholine), intense exercise, and exposure to elevated environmental temperatures 5 .…”

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

“…SLN not only creates an energy demand in the muscle by inducing futile ATP hydrolysis by SERCA, it can also increase mitochondrial ATP synthesis and mitochondrial biogenesis by affecting Ca 2+ dynamics in the cytosol and mitochondria. Therefore, SLN acts as an integrator of several Ca 2+ -mediated functions of the muscle and is a critical determinant of muscle metabolism [81,84,85].…”

Noninvasive and in vivo assessment of upper and lower limb skeletal muscle oxidative metabolism activity and microvascular responses to glucose ingestion in humans

“…Together, these findings reinforce the reproducibility and usefulness of NIRS-VOT technique for assessment of postprandial changes in muscle oxidative metabolism activity. Regarding the difference in the oxidative metabolism responses to glucose ingestion between the arm and the leg muscles found in the current study, it is likely that these findings are justified by differences in the training status and/or the fibre composition of the upper vs lower limbs (Periasamy et al 2017;Pogliaghi et al 2006). Regarding the training status, the majority of the individuals in the current study reported to be engaged in upper and lower limb resistance training; however, the leg muscles are likely to be exposed to additional contractile activity (i.e.…”