Changes observed in proton leak, UCP expression, and circulating hormones appear to influence metabolic efficiency and energy expenditure. In the context of energy restriction, the observed changes are likely to make weight loss increasingly challenging and promote weight regain. It has been reported that females have more BAT than males , and that energy-restricted female rats see greater decreases in BAT mass and UCP-1 than males , indicating a potential sex-related difference in uncoupled respiration during weight loss. Subjects identified as “diet-resistant” show decreased proton leak and
UCP-3 expression compared to “diet-responsive” subjects during maintenance of a reduced bodyweight . Brigatinib solubility dmso More research is needed to determine if these differential responses to hypocaloric diets
make sustained weight loss more difficult for females and certain predisposed “diet-resistant” individuals. While future research may improve our understanding of the magnitude and relative importance of mitochondrial adaptations to energy restriction, current evidence suggests that increased mitochondrial efficiency, and a decline in uncoupled respiration, might serve to decrease the energy deficit in hypocaloric conditions, making weight maintenance and further weight reduction more challenging. Practical applications for weight loss in athletes Hypocaloric diets induce a number of adaptations that serve to prevent further weight loss and conserve energy. It is likely that the magnitude of these adaptations are proportional to the size of the energy deficit, so it is recommended see more to utilize the smallest possible deficit that yields appreciable weight loss. This may decrease the rate of weight loss, but attenuate unfavorable adaptations that challenge successful reduction of fat mass. Weight reduction should be viewed as a stepwise process in this context; as weight loss begins to plateau, energy
intake or expenditure should not be adjusted to “re-open” the energy deficit. Large caloric deficits are also likely to induce greater losses of LBM [66, 67] and compromise athletic performance and recovery [68, 69], which are of critical importance to athletes. Participation in a structured resistance VX-689 mouse training program  and sufficient protein intake [35–37] are also likely to attenuate losses in LBM. Additionally, high protein diets (≥25%PRO) are associated with increased satiety and thermogenesis, making them a better option for the calorie-restricted athlete . In the world of physique sports, periodic “refeeding” has become common in periods of extended dieting. A refeed consists of a brief overfeeding period in which caloric intake is raised slightly above maintenance levels, and the increase in caloric intake is predominantly achieved by increasing carbohydrate consumption.