Intersection of Exercise and Estrogen in Weight Regain After Weight Loss

项目2 -项目总结

Project 2 – Project Summary Over 60% of adults are overweight or obese. Obesity is particularly problematic in women who experience unique physiological changes over their lifespan (e.g., menopause). While many weight-loss strategies exist, weight regain after weight loss remains the largest barrier to successfully treating obesity. Regular exercise is one of the most potent strategies for preventing weight regain after weight loss. We previously developed a preclinical model showing that regular exercise reduces caloric intake during weight regain after weight loss. Importantly, the exercise-induced reduction in caloric intake is observed in males and ovariectomized females but not in intact/cycling female rats. In males, we have shown that regular exercise suppresses the drive to overeat and potentiates energy expenditure above and beyond the cost of the exercise bout. The overall objective of this proposal is to determine how exercise counters the biological drive to regain weight and elucidate the sexual dimorphic response. To achieve this objective, we propose to investigate known mechanisms of appetite and energy expenditure regulation that are thought to mediate the sex differences and explore a novel role for the tryptophan-kynurenine (TRP-KYN) pathway in regulating energy balance in this context. In Aim 1, we will examine sex differences, the effect of ovariectomy, and the impact of exercise on post-prandial gut hormone responses and eating behaviors and during weight regain. We hypothesize that exercise is modulating gut hormone peptides to exert beneficial feeding effects during weight regain after weight loss and that the presence of estrogen interferes with this modulation in intact females to sustain weight regain. In Aim 2, we will determine the impact of ovariectomy and estrogen add-back on exercise-induced energy expenditure during weight regain after weight loss. We hypothesize that the exercise-induced increase in energy expenditure is linked to its ability to enhance the capacity to oxidize fat, which is inherently higher in females due to estrogen. We suspect the presence of estrogen in intact females and ovariectomized females with estrogen add-back will diminish the impact of exercise on dietary fat oxidation and energy expenditure. In addition to testing these hypotheses, our studies will provide valuable information about TRP-KYN pathway metabolites and their role in mediating the effects of sex differences, the loss of ovarian function, and the beneficial effects of exercise training. Observations from these studies will provide insight into the mechanisms of the sexual dimorphic response to exercise during weight regain and identify novel targets and strategies to facilitate weight loss maintenance more effectively.