CNS-periphery relationships and body weight homeostasis: influence of the glucocorticoid status

The obesity-like effects produced by the chronic intracerebroventricular (i .c.v.) neuropeptide Y (NPY) infusion in normal rats require the presence of glucocorticoids, as none of them occurs when NPY is similarly infused in a drenalectomized rats. NPY effects are present again when i.c.v. NPY is infu sed together with i.c.v. dexamethasone in adrenalectomized animals. The inh ibitory effect of leptin on food intake and body weight observed when the h ormone is i.c.v. administered to normal rats is markedly enhanced and longe r lasting when the same dose of leptin is i.c.v. administered to adrenalect omized rats. Glucocorticoid administration to adrenalectomized rats dose-de pendently reduces, then abolishes, this potent effect of leptin. Thus, gluc ocorticoids limit leptin-induced effects. The chronic i.c.v, infusion of gl ucocorticoids (dexamethasone) to normal rats produces an obesity syndrome w ith its several abnormalities. This appears to be due to glucocorticoid-eli cited increases in hypothalamic NPY levels together with decreases in those of CRH. Thus, the status of the hypothalamo-pituitary-adrenal axis and related gluc ocorticoid output is a relevant facet of body weight homeostasis. It may be a deleterious environmental factor responsible for the development of obes ity, insulin as well as leptin resistance, and type 2 diabetes.