SAT-586 Cold-Acclimation Prevents the Onset of Glucocorticoid-Induced Adipose Dysfunction in Male Mice

Glucocorticoid (GC) excess, either endogenously or exogenously, has been causally linked to the development of chronic diseases such as obesity and type-2 diabetes mellitus. Continuously elevated GC levels result in an expansion of white adipose tissue (WAT) depots and a dramatic decrease in the thermogenic capacity in brown and beige adipose tissue (BAT and BeAT, respectively). Herein we aimed to examine the interaction between GCs and the sympathetic nervous system (SNS) in the regulation of WAT, BAT, and BeAT. To this end, we utilized an altered environmental temperature as a non-invasive method for the modulation of sympathetic activity - cold is an activator of SNS-mediated non-shivering thermogenesis. Thus, during a 4-week treatment with either corticosterone or placebo, 10-week-old male C57BL/6NRj mice were maintained at two different temperature levels: 29°C (thermoneutrality) or 13°C (cold temperature). Body weight, as well as energy and water intake, were monitored throughout the study. At sacrifice, serum and adipose tissues were collected for analysis. GC-exposed mice showed a marked increase in circulating corticosterone concentrations compared to placebo controls with no appreciable difference between temperature levels. At thermoneutrality, GC-treated mice gained more weight and consumed more food than their placebo-treated littermates. This GC-induced body weight gain was accompanied by increased (visceral & subcutaneous) WAT weight as well as adipocyte hypertrophy. Interestingly, cold-acclimatized mice showed a marked reduction in GC-induced weight gain, hyperphagia, and fat accumulation. Moreover, the GC-induced rise in blood glucose and serum insulin concentrations - readily observed when mice were maintained at thermoneutrality - was absent in cold-exposed animals. In addition, GC treatment at thermoneutrality resulted in increased lipid deposition and decreased UCP1 expression in BAT, the ‘whitening’ of BAT. This GC-induced loss of thermogenic capacity was profoundly reduced in cold-adapted mice. Across all groups, UCP-1 protein levels in BAT closely correlated (r(2) = 0.70, p < 0.0001) with those of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. These results indicate that cold-acclimation prevents the development of GC-induced metabolic dysfunction in mice. Thus, environmental temperature is a potent modulator of GC-induced adiposity and body weight gain, potentially via an interaction between SNS and GC signaling.