Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice

Abstract

Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( uncoupling protein 1 (UCP1)-based) and skeletal muscle ( sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild severe cold adaptation by employing UCP1 and SLN mice. Interestingly, adaptation of SLN mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes.

Convergent neuronal projections from paraventricular nucleus, parabrachial nucleus, and brainstem onto gastrocnemius muscle, white and brown adipose tissue in male rats

“…These are well‐described thermogenic sites, which utilize distinct mechanisms of heat production; however, recruitment of heat production in both tissues during cold exposure is activated by the autonomic nervous system (Bal, Maurya, et al, ). Both BAT‐ and muscle based, nonshivering thermogenesis are equally recruited during adaptation to mild and severe cold, and loss of heat production from one tissue pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic tissues (Bal, Singh, et al, ). Both skeletal muscle and WAT function as repositories for metabolites and have intrinsic pathways for storing (protein synthesis, lipogenesis) and mobilization (proteolysis, lipolysis).…”

“…These are well-described thermogenic sites, which utilize distinct mechanisms of heat production; however, recruitment of heat production in both tissues during cold exposure is activated by the autonomic nervous system . Both BAT-and muscle based, nonshivering thermogenesis are equally recruited during adaptation to mild and severe cold, and loss of heat production from one tissue pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic tissues (Bal, Singh, et al, 2017 There is some precedent for the concept of convergent target tissue innervation involving muscles and other tissues. For example, Pérez et al (2011) delineated the hierarchy of the anatomical connections among diverse brain regions involved in motor and autonomic elements of feeding.…”

“…In starvation, lipolysis, proteolysis, and gluconeogenesis are co‐activated to generate fuels; similar coordination is also observed in responses either to injury or to immune activation. Likewise, shivering and nonshivering thermogenesis in muscle and nonshivering thermogenesis in BAT are part of integrated response to cold exposure (Bal, Maurya, Singh, Wehrens, & Periasamy, ; Bal, Maurya, et al, ; Bal, Singh, et al, ). The energetic processes executed by BAT as well as skeletal muscle work require a readily available fuel supply, including glucose and WAT‐derived fatty acids (Townsend & Tseng, ).…”

“…Likewise, shivering and nonshivering thermogenesis in muscle and nonshivering thermogenesis in BAT are part of integrated response to cold exposure (Bal, Maurya, Singh, Wehrens, & Periasamy, 2016;Bal, Singh, et al, 2017). The energetic processes executed by BAT as well as skeletal muscle work require a readily available fuel supply, including glucose and WAT-derived fatty acids (Townsend & Tseng, 2014).…”

Body temperature control in rats by muscle tone during rest or sleep

“…[16][17][18][19][20] A representative statement is "more anaerobic muscles, high in type II fibers, tend to shiver in bursts whereas those relying more on aerobic metabolism, high in type I fibers, shiver more continuously". [23][24][25][26][27] Muscle tone has been described as resting mechanical and EMG activity and shown to increase significantly in resting human quadriceps muscles at ambient temperatures below 21.5°C by McKay et al, 28 who write: "An accepted model is that resting muscle is electrically and mechanically inactive at room temperature, that cooling provokes invisible microvibrations called thermoregulatory tonus, that severe cooling causes visible shivering, and that these are simply degrees of the same phenomenon (Blatteis et al, 2001; Haider and Lindsley 1964; Kleinebeckel and Klussman 1990)". By being included in the term shivering, muscle tone often goes unmentioned as a possible separate independent heat producing mechanism, as in a recent review of central control of body temperature 22 or in studies of NST in skeletal muscle.…”