Food restriction is the most effective modulator of oxidative stress and it is believed that a reduction in caloric intake per se is responsible for the reduced generation of reactive oxygen species (ROS) by mitochondria. Hydrogen peroxide (H(2)O(2)) generation and oxygen consumption (O(2)) by skeletal muscle mitochondria were determined in a peculiar strain of rats (Lou/C) characterized by a self-low-caloric intake and a dietary preference for fat. These rats were fed either with a standard high-carbohydrate (HC) or a high-fat (HF) diet and the results were compared to those measured in Wistar rats fed a HC diet. H(2)O(2) production was significantly reduced in Lou/C rats fed a HC diet; this effect was not due to a lower O(2) consumption but rather to a decrease in rotenone-sensitive NADH-ubiquinone oxidoreductase activity and increased expression of uncoupling proteins 2 and 3. The reduced H(2)O(2) generation displayed by Lou/C rats was accompanied by a significant inhibition of permeability transition pore (PTP) opening. H(2)O(2) production was restored and PTP inhibition was relieved when Lou/C rats were allowed to eat a HF diet, suggesting that the reduced oxidative stress provided by low caloric intake is lost when fat proportion in the diet is increased.