Chronic cold acclimation increases thermogenic capacity, non-shivering thermogenesis and muscle citrate synthase activity in both wild-type and brown adipose tissue deficient mice

Abstract

The purpose of this study was to determine whether chronic cold exposure would increase the aerobic capacity of skeletal muscle in UCP-dta mice, a transgenic line lacking brown adipose tissue (BAT). Wild type and UCPdta mice were acclimated to either warm (23 °C), or cold (4 °C) conditions. Cold increased muscle oxidative capacity nearly equivalently in wild-type and UCP-dta mice, but did not affect the respiratory function of isolated mitochondria. Summit metabolism (V̇ O2summit) and norepinephrine-induced thermogenesis (V̇ O2NST) were significantly lower in UCP-dta mice relative to wild-type mice regardless of temperature treatment, but both were significantly higher in cold relative to warm acclimated mice. BAT mass was significantly higher in the cold relative to warm acclimated wild-type mice, but not in cold acclimated UCP-dta mice. BAT citrate synthase activity was lower in transgenic animals regardless of acclimation temperature and BAT citrate synthase activity per depot was significantly higher only in the cold acclimated wild-type mice. Muscle citrate synthase activity was increased in both genotypes. As defects in muscle oxidative function have been observed with obesity and type 2 diabetes, these results suggest that chronic cold exposure is a useful intervention to drive skeletal muscle oxidative capacity in mouse models of obesity.

Brown adipose tissue dynamics in wild-type and UCP1-knockout mice: in vivo insights with magnetic resonance

“…In the present study, we showed a thermogenic response to NA which was enhanced following cold acclimation, indicating an adaptive increase of NST despite the lack of UCP1 in brown adipocytes. In accordance with our results, a thermogenic response to NA in UCP1-KO and UCP1-dta mice has been described previously ( 23,72 ). In contrast, Golozoubova et al ( 24 ), Nedergaard et al ( 71 ), and Cannon and Nedergaard ( 73 ) did not observe an increase in the noradrenergic thermogenic response in these mice following cold acclimation at 18°C and therefore defi ne "adaptive NST" as strictly limited to UCP1-mediated uncoupling of oxidative phosphorylation in brown adipocytes .…”

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

“…The present data, along with the results of other studies (Meyer et al, 2010;Mineo et al, 2012), demonstrate increased oxidative metabolism in skeletal muscle after prolonged cold exposure; however, the physiological significance and the contribution of shivering to total thermogenesis, when non-shivering is activated, remain to be elucidated. In addition, our results show a signaling cascade leading to the training phenotype of skeletal muscle, suggesting the potential benefit of prolonged cold exposure and potential molecular targets in the management of metabolic disorders including obesity and type II diabetes.…”

“…In contrast to the clear role of skeletal muscle shivering thermogenesis in thermoregulation early in cold acclimation, its role during prolonged cold exposure, when nonshivering is activated, is not clear. Recent data showed that sustained cold exposure in animals with brown adipose tissue causes metabolic and structural changes in skeletal muscle that indicate their shivering activity (Meyer et al, 2010;Mineo et al, 2012), similar to those observed following endurance exercise training (Schaeffer et al, 2003). It is known that shivering-related metabolic recruitment, in terms of fuel selection, can be achieved in three ways: (1) by recruitment of specific subpopulations of fibers within the same muscle; (2) by recruitment of muscles varying in fiber composition; and (3) by recruitment of different metabolic pathways within the same fibers.…”

Cold adaptation overrides developmental regulation of sarcolipin expression in mice skeletal muscle: SOS for muscle-based thermogenesis?

“…2E). It has been suggested by previous studies that cold acclimation increases the percentage of slow fibers and oxidative capacity in the skeletal muscles (Bruton et al, 2010;Mineo et al, 2012) and, therefore, a higher SERCA2a level may support the physiological needs of such muscles. We propose that as SLN-mediated thermogenesis demands more ATP, muscles having a high oxidative capacity are better suited to recruit muscle-based NST.…”