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。肥胖症在经历过 在他们的一生中(例如，更年期)发生独特的生理变化。虽然有很多减肥策略， 减肥后体重恢复仍然是成功治疗肥胖症的最大障碍。经常锻炼是 这是预防减肥后体重回升的最有效策略之一。我们之前开发了一种 临床前模型显示，在减肥后体重恢复期间，定期锻炼可以减少卡路里摄入量。 重要的是，在男性和摘除卵巢的女性中，可以观察到运动导致的卡路里摄入量减少。 但在完整/骑行的雌性大鼠中则不是。在男性中，我们已经证明，有规律的锻炼会抑制 暴饮暴食会增加能量消耗，超出锻炼的成本。整体而言 这项建议的目的是确定运动如何对抗恢复体重的生物动力 并解说性二形性反应。为了实现这一目标，我们建议调查已知 食欲和能量消耗调节的机制，被认为是调节性别差异和 探索色氨酸-犬尿氨酸(Trp-Kyn)通路在调节能量平衡中的新作用 背景。 在目标1中，我们将检查性别差异，卵巢切除的效果，以及运动对 餐后肠道激素反应和饮食行为，以及在体重恢复期间。我们假设 这项运动正在调节肠道激素多肽，以在体重恢复期间发挥有益的喂养作用 体重减轻，雌激素的存在干扰了保持体重的完整女性的这种调节 重获新生。 在目标2中，我们将确定卵巢切除和雌激素补充对运动诱导的影响。 在减肥后，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，这是天生的 由于雌激素作用，女性的性激素水平较高。我们怀疑完整的女性和摘除卵巢的女性体内存在雌激素 补充雌激素的女性将减少运动对饮食脂肪氧化和能量的影响 支出。 除了检验这些假说外，我们的研究还将提供有关trp-kyn通路的有价值的信息。 代谢物及其在调节性别差异、卵巢功能丧失和 运动训练的有益效果。这些研究的观察结果将为我们提供对 体重恢复和识别新靶点期间运动的性二态反应的机制 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.