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...

High fat diets (HFD) usually lead to hyperphagia and body weight gain. However, macronutrient proportions in the diet can modulate energy intake and body fat deposition. The aim of the study was to investigate muscle and liver oxidative metabolism in response to an isocaloric intake of a HFD and to elucidate the possible gender-dependent response. Eight week-old male and female rats were fed either standard chow or HFD for 14 weeks. Energy intake, body weight and whole animal oxygen consumption were determined periodically. Mitochondrial oxygen consumption, hydrogen peroxide production, TBARS levels, Cytochrome-c-oxidase, Citrate synthase and antioxidant enzyme activities were measured in muscle and liver. UCP1 and UCP3 protein levels were analyzed in brown adipose tissue and muscle, respectively. Male rats showed higher energy efficiency, enhanced adiposity, greater hydrogen peroxide production and less effective antioxidant machinery compared to females. HFD feeding increased energy expenditure but did not modify either tissue oxidative metabolism or oxidative damage in either gender. HFD animals over-expressed uncoupling proteins in order to maintain energy balance (brown adipose tissue UCP1) and to avoid oxidative stress (skeletal muscle UCP3), thus counteracting the alterations induced by the modification of the proportion of macronutrients in the diet.

Muscle resistance to insulin plays a key role in the metabolic dysregulation associated to obesity. A pro-inflammatory and pro-oxidant status has been proposed to be the link between dietary obesity and insulin resistance. Given the gender differences previously found in mitochondrial function and oxidative stress, the aim of the present study was to investigate whether this gender dimorphism leads to differences in the development of high-fat-diet-induced insulin resistance in rat skeletal muscle. Male and female rats of 15 months of age were fed with a high-fat-diet (32% fat) for 14 weeks. Control male rats showed a more marked insulin resistance status compared to females, as indicated by the glucose tolerance curve profile and the serum insulin, resistin and adiponectin levels. High-fat-diet feeding induced an excess of body weight of 16.2% in males and 38.4% in females, an increase in both muscle mitochondrial hydrogen peroxide production and in oxidative damage, together with a decrease in the Mn-superoxide dismutase activity in both genders. However, high-fat-diet fed female rats showed a less marked insulin resistance profile than males, higher mitochondrial oxygen consumption and cytochrome c oxidase activity, and a better capacity to counteract the oxidative-stress-dependent insulin resistance through an overexpression of both muscle UCP3 and GLUT4 proteins. These results point to a gender dimorphism in the insulin resistance status and in the response of skeletal muscle to high-fat-diet feeding which could be related to a more detrimental effect of age in male rats.

Brown adipose tissue (BAT) thermogenesis is inhibited during late-pregnancy and lactation in the rat. However, scarce information concerning BAT functionality during mid-pregnancy is available. The aim of this work was to investigate uncoupling proteins and leptin expression during placentation in rat BAT as well as other key parameters in the thermogenic function of the tissue. BAT mitochondrial content was found to be reduced 50% in 11 and 13 day pregnant rats as compared to nonpregnant controls, although uncoupling protein 1 (UCP1) content was not modified. Furthermore, UCP3 mRNA levels were found to be highly increased during this period. β₃-adrenergic receptor (β₃-AR) decreased expression resulted in a higher α₂/β₃ ratio. Finally, leptin mRNA levels in BAT were found to be 3-fold up-regulated in pregnant animals. In conclusion, we show the existence of profound changes in thermogenic features in BAT during gestational days 11 and 13, pointing to the importance of this tissue during mid-pregnancy.