Skeletal muscle non‐shivering thermogenesis in hibernating Arctic Ground Squirrels

Abstract

All mammals depend on heat producing mechanisms to maintain homeostasis. Skeletal muscle shivering and brown adipose tissue (BAT) uncoupling through the expression of uncoupling protein 1 (UCP‐1) are the identified major sources of heat production, though recently, skeletal muscle has also been highlighted as a thermogenic source. Skeletal muscle nonshivering heat production occurs via sarcolipin (SLN) uncoupling of sarcoendoplasmic reticulum (SR) calcium ATPase (SERCA)‐mediated ATP hydrolysis. SLN may play a significant role in hibernating animals due to the wide temperature range that requires regulation. A thermoregulatory mechanism needs to be in place to suppress heat production during hibernation and also initiate rapid thermogenesis during arousal. We hypothesized that skeletal muscle uncoupling driven by SLN activity is a significant source of thermogenesis and inhibiting this pathway can alter the metabolic rate during hibernation in Arctic ground squirrels (AGS). Specifically, this work aimed to elucidate the role of skeletal muscle SLN uncoupling and its connection with BAT heat production in thermoregulation and metabolic control during temperature fluctuations. AGS were treated with inhibitors of BAT‐uncoupling or skeletal muscle‐uncoupling during hibernation to assess skeletal muscle and BAT ability to aid in heat production. Rate of temperature increase and changes in VO2 were compared to internal controls during inter‐bout arousals to quantify the effect of suppressing BAT or skeletal muscle uncoupling throughout hibernation. Results show that suppressing skeletal muscle uncoupling by SLN causes a significant reduction in metabolic rate during AGS rewarming. Interestingly, inhibition of BAT thermogenesis did not reduce metabolic rate. Inhibition of thermogenic sources highlighted the importance of SLN uncoupling and metabolism in thermogenesis and systemic thermoregulation. Thermogenesis control is directly linked to metabolic rate and energy loss regulation, and thus influencing thermoregulation processes has the potential for translation to innovative treatments for obesity and other diseases and conditions relevant to metabolism.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103395. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.