Dexamethasone reduces energy expenditure and increases susceptibility to diet‐induced obesity in mice

OBJECTIVE: To investigate how long-term treatment with dexamethasone affects energy expenditure and adiposity in mice and whether this is influenced by feeding on a high-fat diet (HFD). DESIGN AND METHODS: Mice were placed on a HFD for 2 weeks and started on dexamethasone at 5 mg/kg every other day during the next 7 weeks. RESULTS: Treatment with dexamethasone increased body fat, an effect that was more pronounced in the animals kept on HFD; dexamethasone treatment also worsened liver steatosis caused by the HFD. At the same time, treatment with dexamethasone lowered the respiratory quotient in chow-fed animals and slowed nightly metabolic rate in the animals kept on HFD. In addition, the acute VO2 acceleration in response to β3 adrenergic-stimulation was significantly limited in the dexamethasone-treated animals, as a result of marked decrease in UCP-1 mRNA observed in the brown adipose tissue of these animals. CONCLUSIONS: Long-term treatment with dexamethasone in a mouse model of diet-induced obesity decreases brown adipose tissue thermogenesis and exaggerates adiposity and liver steatosis.