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A Single Intracerebroventricular Injection of Dexamethasone Elevates Food Intake and Plasma Insulin and Depresses Metabolic Rates in Adrenalectomized Obese (ob/ob) Mice^1,2,

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824-1224

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.

KEY WORDS: • genetically obese (ob/ob) mice • glucocorticoid injection • metabolic rate • food intake • plasma insulin

¹ Supported by NIH grant DK-15847 and the Michigan State University Agricultural Experiment Station

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 25 July 1994. Revision accepted 10 November 1994.