Acute changes in the response to peripheral leptin with alteration in the diet composition

Dietary induced obesity in rodents is associated with a resistance to lepti n. We have investigated the hypothesis that dietary fat per se alters the f eeding response to peripheral leptin in rats that were fed either their hab itual high- or low-fat diet or were naively exposed to the alternative diet . Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-de prived rats were given either leptin (0.5 mg/kg body wt ip) or saline, afte r which they were provided with either their familiar diet or the alternati ve diet. Food intake of rats adapted and tested with the low-fat diet was r educed 4 h after leptin injection, whereas rats adapted and tested with a h igh-fat diet did not respond to leptin. Leptin was injected again 1 and 5 d ays after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat die t-adapted rats were switched to a high- fat diet, the leptin inhibitory res ponse was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic n europeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obe sity, may induce leptin resistance within a short time of exposure to a hig h-fat diet.