Intersection of Exercise and Estrogen in Weight Regain After Weight Loss

运动与雌激素在减肥后体重恢复中的交叉点

• 批准号: 10712610
• 负责人: Paul S. Maclean
• 金额: $ 29.55万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712610
• 关键词: Acylation; Adipose tissue; Appetite Regulation; Attenuated; Back; Bioenergetics; Biological; Body Weight; Body Weight Changes; Body Weight decreased; Collaborations; Darkness; Deposition; Desire for food; Diet; Dietary Fats; Disease; Eating; Eating Behavior; Energy Intake; Energy Metabolism; Estradiol; Estrogens; Exercise; Exhibits; Fatty acid glycerol esters; Female; Foundations; Hormones; Injections; Intake; Kynurenine; Light; Link; Lipids; Liver; Longevity; Maintenance; Mediating; Menopause; Metabolism; Molecular Profiling; Muscle; Obesity; Observational Study; Ovarian; Ovariectomy; Pancreas; Pathway interactions; Peptide YY; Physiological; Pre-Clinical Model; Punch Biopsy; Rattus; Regulation; Relapse; Role; Sex Differences; Testing; Therapeutic; Tissues; Tracer; Tryptophan; Weight; Weight Gain; Weight maintenance regimen; Woman; Women' s Health; cardiometabolism; cost; cytokine; energy balance; exercise training; experience; feeding; ghrelin; glucagon-like peptide 1; gonad function; insight; lipid biosynthesis; male; men; neural; novel; obesity treatment; overweight adults; oxidation; peptide hormone; pre-clinical; prevent; response; sedentary; sex; sexual dimorphism; transcriptome sequencing

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.

项目2 - 项目摘要 超过60％的成年人超重或肥胖。肥胖在经历的女性中尤其有问题 在他们的寿命（例如更年期）中的独特身体变化。尽管存在许多减肥策略，但 减肥后的体重仍然是成功治疗肥胖症的最大障碍。定期运动是 减肥后，预防体重的最潜在策略之一仍然是。我们以前开发了一个 临床前模型表明，定期运动会减少体重减轻后体重的摄入量。 重要的是，在男性和卵巢雌性中观察到运动引起的热量摄入量的减少 但没有完整/骑自行车的雌性大鼠。在男性中，我们表明定期运动会抑制 暴饮暴食和潜在的能源消耗超出了锻炼的成本。总体 该提议的目的是确定运动如何反驳生物学驱动器以保持体重 并阐明性二态反应。为了实现这一目标，我们建议调查已知的 食欲和能源消耗的机制被认为可以调解性别差异和 探索色氨酸 - 京夜氨酸（TRP-KYN）途径在控制能量平衡中的新作用 语境。 在AIM 1中，我们将检查性别差异，卵巢切除术的影响以及运动对 后肠肠龙的反应和饮食行为以及体重仍然存在。我们假设 该练习正在调节肠马辣椒，以在体重减轻期间发挥有益的喂养效果。 体重减轻以及雌激素干扰这种调节以维持体重 恢复。 在AIM 2中，我们将确定卵巢切除术和雌激素补充对运动引起的影响 体重减轻后体重减轻后的能量消耗。我们假设锻炼引起的 能源消耗的增加与增强氧化物脂肪能力的能力有关，这是固有的 我们怀疑完整的女性和卵巢切除术中存在雌激素 雌激素添加后背的女性将减少运动对饮食脂肪氧化和能量的影响 支出。 除了测试这些假设外，我们的研究还将提供有关TRP-KYN途径的宝贵信息 代谢物及其在介导性别差异的影响，卵巢功能丧失和 运动训练的有益影响。这些研究的观察将为您洞悉 性重量期间对锻炼的性二态反应的机制仍然存在，并确定新的目标和 更有效地促进减肥的策略。