Intersection of Exercise and Estrogen in Weight Regain After Weight Loss

项目2 -项目摘要 超过60%的成年人超重或肥胖。肥胖在经历过性行为的女性中尤其成问题。 在其寿命期间的独特生理变化（例如，绝经期）。虽然有许多减肥策略， 减肥后体重反弹仍然是成功治疗肥胖症的最大障碍。经常运动是 减肥后防止体重反弹的最有效策略之一。我们以前开发了一个 临床前模型显示，定期锻炼可减少体重减轻后体重恢复期间的热量摄入。 重要的是，在男性和卵巢切除的女性中观察到运动引起的热量摄入减少 但在完整/周期性雌性大鼠中没有。在男性中，我们已经表明，定期锻炼会抑制 吃得过饱，并增强能量消耗，超出运动回合的成本。整体 这项建议的目的是确定运动如何对抗恢复体重的生物驱动力 并阐明性二型反应。为了实现这一目标，我们建议调查已知的 食欲和能量消耗调节机制被认为是介导性别差异的机制， 探索在这种情况下，TRP-犬尿氨酸（TRP-KYN）通路在调节能量平衡中的新作用。 上下文 在目标1中，我们将研究性别差异，卵巢切除术的影响，以及运动对 餐后肠道激素反应和饮食行为以及体重恢复期间。我们假设 运动是调节肠道激素肽发挥有益的喂养效果，在体重恢复后， 体重减轻，雌激素的存在干扰了完整女性维持体重的这种调节 恢复。 在目标2中，我们将确定卵巢切除术和雌激素补充对运动诱导的 体重减轻后体重恢复期间的能量消耗。我们假设运动引起的 能量消耗的增加与其增强氧化脂肪的能力有关， 由于雌激素的作用，女性的体重更高。我们怀疑雌激素的存在，在完整的女性和卵巢切除 雌激素补充的女性将减少运动对饮食脂肪氧化和能量的影响 支出 除了验证这些假设，我们的研究将提供有关TRP-KYN通路的有价值的信息 代谢物及其在介导性别差异、卵巢功能丧失和卵巢功能障碍中的作用。 运动训练的有益效果。这些研究的观察结果将提供对 在体重恢复过程中对运动的性二态反应的机制，并确定新的目标， 更有效地促进减肥维持的策略。

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.