Muscle nonshivering thermogenesis in a feral mammal

Julia Nowack,Thomas Ruf,Johanna Painer,Claudia Bieber,Perica Jurcevic,Gabrielle Stalder,Sebastian G Vetter,Steve Smith,Minh Hien Le,Maria Kral,Walter Arnold

doi:10.1038/s41598-019-42756-z

Abstract

Muscle nonshivering thermogenesis (NST) was recently suggested to play an important role in thermoregulation of species lacking brown adipose tissue (BAT). The mechanism, which is independent of muscle contractions, produces heat based on the activity of an ATPase pump in the sarcoplasmic reticulum (SERCA1a) and is controlled by the protein sarcolipin. To evaluate whether muscle NST could indeed play an important role in thermoregulation in species lacking BAT, we investigated the thermogenic capacities of newborn wild boar piglets. During cold exposure over the first 5 days of life, total heat production was improved while shivering intensity decreased, indicating an increasing contribution of NST. Sampling skeletal muscle tissue for analyses of SERCA activity as well as gene expression of SERCA1a and sarcolipin, we found an age-related increase in all three variables as well as in body temperature. Hence, the improved thermogenesis during the development of wild boars is not due to shivering but explained by the observed increase in SERCA activity. Our results suggest that muscle NST may be the primary mechanism of heat production during cold stress in large mammals lacking BAT, strengthening the hypothesis that muscle NST has likely played an important role in the evolution of endothermy.

Highlights

It was long believed that species without thermogenic functional UCP1 rely solely on shivering, a process that on its own is insufficient for the maintenance of a stable Tb during cold exposure in knockout mice[11]
Studies on laboratory mice have shown that muscle nonshivering thermogenesis (NST) can compensate for the loss of UCP1, but muscle NST in wild type mice is largely masked by heat production in BAT30,31
We investigated whether muscle NST is an important and effective mechanism to generate heat in feral, mammals lacking brown adipose tissue (BAT), using newborn wild boars (Sus scrofa), naturally lacking BAT32 and UCP1-dependent NST33,34 as model species

Summary

Introduction

It was long believed that species without thermogenic functional UCP1 rely solely on shivering, a process that on its own is insufficient for the maintenance of a stable Tb during cold exposure in knockout mice[11]. ATP hydrolysis by SERCA1a can be uncoupled from actual transmembrane transport of Ca2+ by the regulatory protein sarcolipin (SLN) causing the release of the Ca2+-ions bound to SERCA back to the cytoplasmic side of the membrane (so called “slippage”) rather than into the sarcoplasmic reticulum[26] This results in increased ATP hydrolysis and heat production in muscle through SERCA1a activity without actual Ca2+-transport and without muscle contraction[13,26,27,28,29]. Studies on laboratory mice have shown that muscle NST can compensate for the loss of UCP1, but muscle NST in wild type mice is largely masked by heat production in BAT30,31 This raises the question whether the thermogenic capacity of muscle NST alone can enable mammals to maintain a stable Tb under cold conditions. If heat production is based on muscle NST, expression levels of SERCA1a and sarcolipin as well as SERCA activity should be elevated during cold exposure

Methods

Results

Conclusion