A single intracerebroventricular injection of dexamethasone elevates food intake and plasma insulin and depresses metabolic rates in adrenalectomized obese (ob/ob) mice.

A single intracerebroventricular (ICV) injection of dexamethasone rapidly (within 30 min to 3 h) increases plasma insulin and suppresses oxygen consumption in adrenalectomized ob/ob mice with minimal effects in lean mice. Food intake of these adrenalectomized ob/ob mice was unaffected by ICV dexamethasone during these short-term studies. However, in a longer-term study with adrenalectomized gold thioglucose-lesioned obese mice, food intake increased fourfold 6-8 d after a single ICV injection of dexamethasone. We have now further examined the time course of dexamethasone actions in adrenalectomized ob/ob and lean mice in the 96-h post-injection period. A single ICV injection of dexamethasone increased food intake 32% and plasma insulin 81%, and depressed oxygen consumption 11%, in adrenalectomized ob/ob mice during the 24-h period after injection, without increasing food intake or plasma insulin in lean mice. Oxygen consumption was 14% lower in lean mice 24 and 48 h after dexamethasone injection relative to saline-injected lean mice. Food intake and oxygen consumption in ob/ob mice returned to levels in saline-injected controls at 48 and 72 h after injection, respectively. Oxygen consumption of lean mice also returned to control levels at 72 h post-injection. Plasma insulin concentrations were similar in dexamethasone- and saline-treated ob/ob and lean mice at 96 h post-injection (the only time point examined other than 24 h). A single ICV injection of dexamethasone exerts both rapid (within 30 min to 3 h) and sustained (days) metabolic actions in ob/ob mice.