related differences in energy balance were studied in young Wistar rats fed standard chow pellets either ad libitum or in restricted amounts (60% of ad libitum intake) for 100 days. Caloric intake, indirect calorimetry, organ and adipose tissue weights, energy efficiency, liver mitochondrial respiration rate, and brown adipose tissue (BAT) uncoupling protein-1 (UCP1) content were measured. Ad libitum-fed females showed greater oxygen consumption (V O2) and carbon dioxide production (V CO2) and lower energy efficiency than males. Caloric restriction induced a chronic drop of V O2 and V CO2 in females but not in males over the period studied. Restricted females showed a better conservation of metabolic active organ mass and a greater decrease in adipose depots than restricted males. Moreover, changes of BAT size and UCP1 content suggest that BAT may be the main cause responsible for sex differences in the response of energy balance to caloric restriction. In conclusion, our results indicate that females under caloric restriction conditions deactivate facultative thermogenesis to a greater degree than males. This ability may have obvious advantages for female survival and therefore the survival of the species when food is limiting. brown adipose tissue; sexual dimorphism; uncoupling protein-1; oxygen consumption ENERGY BALANCE DEPENDS ON THE MECHANISMS that regulate and coordinate food intake and the different components of energy expenditure, including basal metabolism, physical activity, and heat production. When food is in short supply, caloric intake is lower than energy expenditure, resulting in a negative energy balance (25). Caloric restriction (CR) is a frequent condition in nature; hence, throughout evolution, organisms have evolved mechanisms to respond and adapt to energy restriction. Several studies have reported that CR and starvation have a consistently greater effect on physical growth in males than in females (10,23,25,26,29,63,64). Furthermore, important sex-associated differences have been found in the response of white adipose mass to CR. These studies suggest that females use energy stored as fat to a greater extent than males (26, 44). However, the loss of lean body mass cannot wholly explain the energy conservation seen when female rats are subjected to CR (26).Restriction of physical activity could be another strategy to improve energy efficiency. Nevertheless, CR rats are as active as ad libitum-fed rats, indicating that they are not economizing their energy by restricting their activity (16,24,38,43).Another possibility to explain changes in energy efficiency related to sex implies differences in heat production. In rodents, nonshivering thermogenesis takes place mainly in brown adipose tissue (BAT), where thermogenesis activity depends on uncoupling protein-1 (UCP1), an inner-membrane mitochondrial protein expressed characteristically in this tissue, the function of which is to dissipate, as heat, the proton gradient energy generated by the respiratory chain (7, 48). These particular energ...