Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat

It has been claimed that factors favoring the development or maintenance of animal or human obesity may include increases in glucocorticoid production or hyperresponsiveness of the hypothalamic-pituitary-adrenal axis. In norm al rats, glucocorticoids have been shown to be necessary for chronic intrac erebroventricular infusion of neuropeptide Y to produce obesity and related abnormalities. Conversely, glucocorticoids inhibited the body weight-lower ing effect of leptin. Such dual action of glucocorticoids may occur within the central nervous system, since both neuropeptide Y and leptin act within the hypothalamus. The aim of this study was to determine the effects of gl ucocorticoids (dexamethasone) given intracerebroventricularly to normal rat s on body weight homeostasis and hypothalamic levels of neuropeptide Y and corticotropin-releasing hormone. Continuous central glucocorticoid infusion for 3 days resulted in marked sustained increases in food intake and body weight relative to saline-infused controls. The infusion abolished endogeno us corticosterone output and produced hyperinsulinemia, hypertriglyceridemi a, and hyperleptinemia, three salient abnormalities of obesity syndromes. C entral glucocorticoid infusion also produced a marked decrease in the expre ssion of uncoupling protein (UCP)-1 and UCP-3 in brown adipose tissue and U CP-3 in muscle. Finally, chronic central glucocorticoid administration incr eased the hypothalamic levels of neuropeptide Y and decreased those of cort icotropin-releasing hormone. When the same dose of glucocorticoids was admi nistered peripherally, it resulted in decreases in food intake and body wei ght, in keeping with the decrease in hypothalamic neuropeptide Y levels. Th ese results suggest that glucocorticoids induce an obesity syndrome in rode nts by acting centrally and not peripherally.