Leptin regulation of prepro-orexin and orexin receptor mRNA levels in the hypothalamus

The aim of this study was to determine the effects of leptin treatment on p repro-orexin and orexin receptor expression in the rat hypothalamus. Adult male rats, food-deprived for 48 and 72 h, were treated one time with vehicl e or leptin (10 mu g, icv). Prepro-orexin mRNA content was measured by semi quantitative RT-PCR, Northern blot, and in situ hybridization; orexin recep tor 1 and 2 mRNA content was quantified by Northern blot and/or semiquantit ative RT-PCR. Our results indicate that leptin inhibits a fasting-induced i ncrease in prepro-orexin mRNA and orexin receptor 1 mRNA levels in the rat hypothalamus, while orexin receptor 2 mRNA levels were unchanged in all sit uations evaluated. These data provide direct evidence for an additional mec hanism of adaptation of the hypothalamus to food deprivation and for a new effect of leptin in the regulation of food intake. (C) 2000 Academic Press.