Estrogen Regulation of Daily Metabolic Rhythms

项目摘要 与肥胖相关的疾病每年导致280万人死亡。术后循环中雌激素的丢失 更年期增加了肥胖的患病率，以及威胁生命的肥胖相关疾病的风险，如 在女性中为心血管疾病和中风。倒班和夜间进食也会增加肥胖的风险。 代谢综合征表明昼夜节律的紊乱会导致代谢功能障碍。这 该项目将确定雌激素如何与昼夜节律系统相互作用，以保护女性免受肥胖和 相关的障碍。在我们之前的研究中，我们证明了昼夜节律的中断， 高脂饮食的摄入和雄性小鼠的肥胖。雄性小鼠会出现严重的饮食诱导肥胖。我们 研究发现，仅在高脂饮食摄入一周后，日常饮食行为的节律 雄性小鼠的肝脏生物钟的时间也迅速提前。在……里面 相比之下，雌性小鼠对饮食诱导的肥胖具有抵抗力。在我们的初步研究中，我们发现高脂肪饮食 不会改变女性的日常饮食行为节奏或肝脏生物钟。因此，我们假设 在高脂饮食期间保持正常的日常代谢节律可以保护人们免受饮食的影响。 女性的诱导性肥胖。这项提议的目的是阐明分子和行为机制。 保护女性的日常节律不受高脂肪饮食的影响。我们的具体目标是(1)确定雌激素是否 调节高脂饮食对雌性小鼠日常节律的影响；以及(2)确定雌激素调节 日常饮食行为的节律可以保护女性免受饮食引起的肥胖。这项工程的完成 将揭示女性免受饮食诱导肥胖的机制，并为发育提供信息 治疗女性肥胖症的新疗法。

Project Summary Obesity-related disorders account for 2.8 million deaths per year. The loss of circulating estrogen after menopause increases the prevalence of obesity and the risk of life-threatening, obesity-related disorders such as cardiovascular disease and stroke in women. Shift work and night-eating also increase the risk of obesity and metabolic syndrome suggesting that disruption of circadian rhythms causes metabolic dysfunction. This project will determine how estrogen interacts with the circadian system to protect females from obesity and related disorders. In our previous studies, we demonstrated a link between disruption of circadian rhythms, consumption of high-fat diet, and obesity in male mice. Male mice develop profound diet-induced obesity. We found that after only one week of high-fat diet consumption, the daily rhythm of eating behavior was immediately altered and the timing of the circadian clock in the liver was robustly advanced in male mice. In contrast, female mice are resistant to diet-induced obesity. In our preliminary studies, we found high-fat diet does not alter the daily rhythm of eating behavior or the liver clock in females. Thus, we hypothesize that retention of normal daily metabolic rhythms during high-fat diet consumption confers protection from diet- induced obesity in females. The goal of this proposal is to elucidate the molecular and behavioral mechanisms that protect daily rhythms from high-fat diet in females. Our specific aims are (1) to determine if estrogen regulates the effects of high-fat diet on daily rhythms in female mice; and (2) to determine if estrogen regulation of the daily rhythm of eating behavior protects females from diet-induced obesity. The completion of this project will reveal mechanisms whereby females are protected from diet-induced obesity and inform the development of novel therapeutics for obesity in women.