Endocrine Abstracts

Glucocorticoids (GC) are one of the most potent anti-inflammatory pharmacological agents. However, owing to their pleiotropic nature, their clinical effectiveness is frequently limited by their deleterious off-target effects. Frequently, metabolic abnormalities arise from GC excess involving the development of dyslipidaemia, insulin resistance and muscle atrophy as well as excessive fat accumulation in both white adipose tissue (WAT) and the liver. In addition, suppressed thermogenic capacity in brown adipose tissue (BAT) has been observed during GC excess in rodents. Cold exposure is an established activator of sympathetic innervation of BAT triggering adaptive thermogenesis and lipid utilisation in BAT as well as WAT. Therefore, our investigation aimed to characterize the interaction between cold-induced thermogenesis and systemic GC excess on the adipose organ. To this end, we treated 32-week-old mice with corticosterone at either 29°C (thermoneutrality) or 13°C (cold temperature). Following 6 weeks of treatment, mice housed at 29°C gained more weight than their temperature-matched controls, which was coupled with excessive accumulation of white fat and consecutive adipocyte hypertrophy. Interestingly, mice maintained in the 13°C environment were protected from GC-driven obesity as well as adipocyte hypertrophy in WAT. Interestingly, the thermogenic capacity, as well as the sympathetic innervation of BAT, was partially preserved in mice maintained at 13°C in spite of corticosterone treatment, whereas mice housed at 29°C showed a considerable reduction in BAT thermogenic capacity and number of sympathetic nerve endings following GC excess. Moreover, treatment with corticosterone at 29°C resulted in increased hepatic lipid accumulation, while livers from mice maintained in the cold showed markedly fewer lipid deposits. On the systemic level, cold adaptation of mice partially prevented the development of GC-induced hyperinsulinemia and hyperleptinemia, both of which were readily observed at 29°C. Taken together, our data demonstrate that prolonged cold exposure prevents the onset of not only GC-induced adipose dysfunction but also related metabolic comorbidities including steatosis of the liver and hyperinsulinemia. Thus, activation of adaptive thermogenesis may be a potential therapeutic target for the prevention of GC-induced metabolic dysfunction.