Food intake-induced leptin secretion modulates hypothalamo-pituitary-adrenal axis response and hypothalamic Ob-Rb expression to insulin administration

The mutation of the ob gene is known to induce a phenotype of obesity accom panied by symptoms including enhanced production of glucocorticoid. Chronic administration to ob/ob mice of leptin, the ob gene product, reverses hype rcorticosteronemia. This establishes a clear relation between adipocyte and hypothalamo-pituitary-adrenal (HPA) axis functions. In the present study w e investigated the acute modulatory effects of food intake-stimulated lepti n secretion on HPA axis activity and hypothalamic leptin receptor (Ob-Rb) e xpression in 24-hour fasting, adult female, BALB/c mice after insulin-induc ed hypoglycemia. Our results indicate that: (1) food supply for 45 min to 2 4-hour fasting mice increased plasma glucose levels and reversed both hyper corticosteronemia and hypoleptinemia; (2) the insulin-induced hypoglycemia produced a marked HPA axis activation in animals with no access to food but this response was fully prevented by food intake and the consecutive incre ase in plasma leptin levels; (3) the inhibitory effect of leptin on the HPA axis response to insulin-induced hypoglycemia was corroborated by i.p. adm inistration of murine leptin, and (4) fasting-induced hypothalamic Ob-Rb ov erexpression is not modulated by insulin itself but by leptin, since increa se in leptin levels by food intake or by administration of exogenous leptin completely reversed this Ob-Rb overexpression. These results confirm the i nhibitory effect of leptin on the HPA axis response to various stress stimu li. They clearly demonstrate that acute food intake in 24-hour fasting mice : (a) rapidly reduced fasting-induced hypercorticosteronemia by enhancing b oth spontaneous and insulin-elicited endogenous leptin secretion; (b) fully prevented HPA axis response to insulin administration, by rapidly increasi ng endogenous leptin secretion and probably also by diminishing the extent and the duration of insulin-induced hypoglycemia, and (c) abolished hypotha lamic Ob-Rb overexpression induced by fasting itself combined with insulin treatment. The present data strongly suggests an inhibitory effect of endog enous leptin on insulin-induced HPA axis response, an interaction relevant to the physiological adaptation to starvation and caloric excess, and furth er supports the pivotal role played by the hypothalamus in restoring homeos tasis in different allostatic states. Copyright (C) 2000 S. Karger AG, Base l.