Nonshivering Thermogenesis in Skeletal Muscle and Adipose Tissue

Nonshivering thermogenesis (NST) is a controlled process by which mammals generate heat in response to cold without muscular contractions. In brown adipose tissue (BAT), heat is produced through mitochondrial uncoupling mediated by uncoupling protein 1 (UCP1), which dissipates the proton gradient to generate warmth. In skeletal muscle, NST relies on the sarcoplasmic reticulum Ca2+-ATPase (SERCA) pump, which can be uncoupled by sarcolipin (SLN) to consume ATP and release heat. These dual pathways interact dynamically: when BAT function is limited or absent, muscle-based NST can be upregulated, and vice versa. Beyond thermoregulation, NST contributes to energy balance, influences lipid and glucose metabolism and offers a potential target for combating obesity and metabolic disorders. Emerging evidence highlights complex regulation by hormonal signals, genetic background and environmental acclimation, underscoring the global importance of understanding both adipose- and muscle-mediated heat production.

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Nonshivering Thermogenesis in Skeletal Muscle and Adipose Tissue publication trend

The graph below shows the total number of articles in nonshivering thermogenesis in skeletal muscle and adipose tissue across all publications each year (not limited to Nature Index journals).

Technical terms

Nonshivering thermogenesis (NST): Heat generation in tissues without shivering, relying on cellular mechanisms that consume ATP to produce warmth.

Brown adipose tissue (BAT): A specialised fat depot rich in mitochondria and UCP1, dedicated to rapid heat production.

Uncoupling protein 1 (UCP1): A mitochondrial membrane protein that dissipates the proton gradient to generate heat instead of ATP.

Sarcoplasmic reticulum Ca2+-ATPase (SERCA): A pump that transports Ca2+ into the sarcoplasmic reticulum, normally using ATP to maintain calcium homeostasis.

Sarcolipin (SLN): A small regulatory protein that binds SERCA and uncouples ATP hydrolysis from Ca2+ transport, leading to heat release.

Mitophagy: The selective degradation of mitochondria by autophagy, crucial for maintaining mitochondrial quality and adapting energy metabolism.

References

1. Sarcolipin Protein Interaction with Sarco(endo)plasmic Reticulum Ca2+ATPase (SERCA) Is Distinct from Phospholamban Protein, and Only Sarcolipin Can Promote Uncoupling of the SERCA Pump*. Journal of Biological Chemistry (2013).
2. Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function*. Journal of Biological Chemistry (2016).
3. Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle. Molecular Metabolism (2023).
4. Cold exposure alters lipid metabolism of skeletal muscle through HIF-1α-induced mitophagy. BMC Biology (2023).
5. Muscle Non-shivering Thermogenesis and Its Role in the Evolution of Endothermy. Frontiers in Physiology (2017).