GLUCOCORTICOIDS IN THE CNS REGULATE BAT METABOLISM AND PLASMA-INSULIN IN OB/OB MICE

Adrenalectomy stimulates depressed brown adipose tissue (BAT) metabolism and decreases hyperinsulinemia in ob/ob mice, with minimal effects in lean mice. A single intracerebroventricular injection of dexamethasone (250 ng) into adrenalectomized ob/ob mice completely reversed the effects of adrenalectomy on BAT thermogenesis as assessed by mitochondrial GDP binding, approximately doubled plasma insulin, lowered whole body metabolic rates by 17%, and increased food intake by 19%. These responses were rapid in onset, with changes in BAT metabolism and plasma insulin occurring within 30 min of dexamethasone injection. Adrenal-ectomized lean mice were much less responsive to dexamethasone than their ob/ob counterparts. The dexamethasone-induced decrease in BAT thermogenesis in adrenalectomized ob/ob mice was associated with an organ-specific decrease in BAT sympathetic nerve activity as assessed by norepinephrine turnover, whereas the dexamethasone-induced increase in plasma insulin was blocked by atropine, suggesting involvement of the parasympathetic nervous system. Intracerebroventricular injection of corticotropin-releasing hormone did not affect BAT thermogenesis in dexamethasone-injected adrenalectomized ob/ob mice but markedly lowered plasma insulin concentrations, possibly by suppression of the parasympathetic nervous system. In conclusion, dexamethasone alters regulation of the autonomic nervous system in ob/ob mice.