Glucocorticoid (GC) excess, either endogenously or exogenously, has been causally linked to the development of chronic and age-related 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 aim to examine the interaction between GCs and the sympathetic nervous system (SNS) in the regulation of WAT, BAT and BeAT.
To this end, sympathetic activity was modulated in vivo by altering environmental temperature. Mice were maintained at three different temperature levels: 29°C (thermoneutrality), 22°C (room temperature) and 13°C (cold temperature), while being treated with either corticosterone or placebo (via the drinking water) for 4 weeks. During treatment body weight as well as energy and water intake were monitored. At sacrifice serum and adipose tissues were collected for analysis.
At thermoneutrality and room temperature, GC-treated mice gained more weight, consumed more food, and accumulated more adipose tissue than their placebo-treated littermates. Interestingly, cold-acclimatized mice showed a marked reduction in GC-induced weight gain, hyperphagia and lipid deposition in adipose tissues, despite similarly elevated levels of circulating corticosterone compared to other experimental groups. Moreover, the GC-induced rise in serum insulin concentrations - readily observed when mice were maintained at thermoneutrality or room temperature - was absent in cold-exposed animals.
Our results demonstrate that cold exposure prevents the development of GC-induced metabolic dysfunction in mice. Thus, environmental temperature is a potent modulator of GC-induced fat accumulation and body weight gain, potentially via an interaction between SNS and GC signaling.