The conflict of thermogenic responses in CD-l mice to chronic hypoxic and cold environments

Abstract

<p>Surviving at high-altitudes requires organisms to endure the combined<br />stresses of cold temperature and low atmospheric oxygen. Maintaining a stable<br />body temperature (Tb) is a constant battle that endotherms must defend when they<br />are subjected to temperatures beyond their thermal neutral zones (TNZ). Once<br />outside their TNZ, they elicit mechanisms of adaptive thermogenesis which<br />stimulate heat production via non-shivering (NST) and shivering thermogenesis<br />(ST). These processes are carried out in brown adipose tissue (BAT) and skeletal<br />muscle, respectively. Uncoupling proteins (UCP) carry out mechanisms of NST<br />by uncoupling substrate oxidation from ATP synthesis to generate heat. Many<br />studies have examined responses in endotherms to cold temperature acclimations<br />as well as episodes of acute hypoxia. However very few studies have looked at<br />the chronic effects of hypoxia and even less have investigated the combined<br />. effects of cold and hypoxia acclimations. Therefore, to address this issue we<br />examined the chronic effect of four weeks of exposure to hypobaric hypoxia (H,<br />480mmHg), cold (C, SOC) and the combination of the two stressors (HC)<br />compared to normoxic thermoneutral controls (N, 28°C) in CD-l mice. Overall<br />we found that HC mice had significantly lower Tb after periods of acclimation<br />while still residing in hypoxia compared to all other treatment groups. However,<br />experiments during acute temperature exposures in normoxia revealed that HC<br />mice were able to increase Tb as well as they demonstrated higher rates of thermal<br />conductance at high ambient temperatures. Investigations into BAT and UCP<br />regulation revealed that HC had a greater amount of BAT mass compared to controls and lower UCPl mRNA expression in BAT but no differences in UCPl<br />protein content. However, HC had lower mitochondrial density indicated by<br />lower activity of citrate synthase in BAT as well as UCP3 mRNA expression.<br />Together results from cold mice suggest that they exhibit an enhanced NST<br />capacity through the up-regulation of BAT mass and UCPl mRNA expression<br />whereas hypoxia inhibits NST response by down-regulation of UCPl and<br />mitochondrial density. Moreover the acclimation to both hypoxia and cold may<br />create barriers on an animal's ability to up-regulate NST in hypoxia by decreasing<br />mitochondrial density, UCPl and 3 mRNA expressions but still allows BAT<br />mechanisms to generate heat through UCPl protein that regulates Tbin normoxia.</p>