The aim of the present study was to elucidate whether the qualitative composition of dietary fat influences plasma leptin and adipose tissue ob gene expression differentially. Two high-fat diets and a diet rich in carbohydrate were each administered both ad libitum and with a 25% energy restriction. The high-fat diets contained 58 energy percent as either monounsaturated FA (MUFA) or saturated FA (SAFA), whereas the carbohydrate-rich diet (CH) contained 7 energy percent as fat. We aimed at obtaining the same final weight for the animals in the ad libitum group as in the energy-restricted groups. This goal was reached at the same time (days 22-24) for all groups except for the ad libitum animals fed on saturated fat (day 36). The plasma leptin concentrations on ad libitum CH and MUFA diets did not differ significantly (24.3 +/- 2.1 and 34.7 +/- 6.7 ng/mL, respectively) whereas the saturated fat diet caused a lower concentration (13.9 +/- 1.9 ng/mL; P < 0.05). Interestingly, no differences in plasma leptin levels between groups were seen in the energy-restricted groups (mean 8.0 +/- 1.0 ng/mL). The type of diet did not alter the ob gene expression in intraabdominal white adipose tissue; however, a lower expression level was found in the energy-restricted groups. The percentage of body fat in the three ad libitum fed groups did not differ (23 +/- 1%). Thus, short-term administration of a diet rich in SAFA suppresses circulating leptin levels without altering the adipose tissue ob gene expression. This indicates that saturated fat may alter protein handling by adipose tissue or the whole body clearance of leptin.