Changes In Hypothalamic Leptin Sensitivity After Acute And Repeated Neurogenic Stress.

Abstract

Neurogenic stress is known to markedly affect energy balance. When repeated, it may alter hypothalamic leptin signaling. We therefore examined, in the hypothalamus, the effects of repeated restraint on the expression of the leptin receptor LRb the regulator of cytokine signaling SOCS3 the stress-induced hormone CRF and the leptin responsive neuropeptides NPY and POMC. Adult male Fisher-344 rats were subjected to acute or repeated restraint stresses (4 h each bout, 2 or 13 days respectively). Selected hypothalamic nuclei were isolated by punches and mRNA expression was assessed by real-time quantitative PCR. Restraint-stress induced a transient drop in daily food intake (from day 1 to 3), a persistent weight loss and a decrease in circulating leptin levels beginning on day 2. Acute restraint rapidly increased LRb mRNA and elicited SOCS3 induction, while the expression of CRF, NPY and POMC was upregulated. After 13 days, all mRNA values had recovered their initial levels, while circulating leptin levels carried on falling. These data suggest a transient hypersensitivity to leptin during acute stress, associated with an adapted response of the orexigenic factor NPY. In contrast, after repeated restraint, neither leptin signaling nor hypothalamic NPY responded to the additional drop in circulating leptin levels, suggesting that chronic neurogenic stress may decrease central leptin sensitivity.