The changes in metabolic efficiency, body composition, and nutrient partitioning induced by high-fat feeding were evaluated in adult rats (90 d of age). The alterations in serum free triiodothyronine, insulin, and leptin levels, as well as in hepatic and skeletal muscle metabolism, were also assessed. Rats were fed either a low- or a high-fat diet for 2 weeks. Relative to the low-fat feeding, energy intake and expenditure, as well as body-energy gain, lipid gain, and energetic efficiency, were increased by the high-fat feeding. Increased serum leptin levels accompanied these variations. A positive correlation between serum leptin levels and percentage of body fat was found in the rats fed the low- or high-fat diet, with a significant divergence between the slope of the regression lines. Furthermore, a negative correlation between serum leptin level and energy intake was found in the rats fed the low-fat diet, while a positive correlation was found in the rats fed the high-fat diet. Finally, the high-fat feeding decreased the hepatic and skeletal muscle mitochondrial oxidative capacity. It is concluded that, in adult rats, a nutritional factor such as a high level of fat in the diet induces obesity, leptin resistance, and impairment of mitochondrial capacity, all phenomena typical of unrestrained aged rats.