Phosphorylation of STAT3 in hypothalamic nuclei is stimulated by lower doses of leptin than are needed to inhibit food intake

Abstract

This experiment investigated which hypothalamic nuclei were activated by a dose of leptin that inhibited food intake. Food intake, energy expenditure, respiratory exchange ratio (RER) and intrascapular brown adipose tissue (IBAT) temperature were measured in male and female Sprague Dawley rats for 36 hours following an intraperitoneal injection of 0, 50, 200, 500 or 1000 mg leptin/kg with each rat tested with each dose of leptin in random order. In both males and females RER and 12 hour food intake and were inhibited only by 1000 mg leptin/kg, but there was no effect on energy expenditure or IBAT temperature. At the end of the experiment pSTAT3 immunoreactivity was measured one hour after injection of 0, 50, 500 or 1000 mg leptin/kg. In male rats the lowest dose of leptin produced a maximal activation of STAT3 in the Arc and nucleus of the solitary tract (NTS). There was no response in the dorsomedial hypothalamus but there was a progressive increase in VMH pSTAT3 with increasing doses of leptin. In female rats there was no significant change in Arc pSTAT3, NTS activation was maximal with 500 mg leptin/kg, but only the highest dose of leptin increased VMH pSTAT3. These results suggest that the VMH plays an important role in the energetic response to elevations of circulating leptin, but do not exclude the possibility that multiple nuclei provide the appropriate integrated response to hyperleptinemia.