Role of Gut Peptides in the Regulation of Energy Balance

动物和人类的能量平衡是由协调能量摄入和输出的因素决定的。众所周知，肥胖是由于摄入的卡路里多于燃烧的卡路里造成的。大约35%的猫狗不是超重就是肥胖。在马和人类中，肥胖及其并发症(如糖尿病)的患病率也在增加。此外，在畜牧业中，将消耗的饲料转化为牛奶和肉类的效率是决定农场盈利能力的关键因素。因此，了解调节能量平衡的基本生物学机制是很重要的。食物被摄入后，肠道会分泌一些肽，这些肽反过来会通知大脑产生饱腹感；然而，肠道调节食物摄入量和体重的潜在机制在很大程度上尚不清楚。我的研究计划的总体目标是从根本上了解肠道分泌的多肽调节能量平衡的生理机制。我们之前已经证明，肠肽YY(PYY)可以减少大鼠的摄食量。在这项提议中，我将通过应用新的方法来解决以下目标来促进我们对PYY调节能量平衡的机制的理解：1)确定餐后从肠道分泌的PYY是否向大脑发出产生饱腹感的信号，研究其发生的机理，并使用大鼠模型确定参与其中的大脑区域；2)确定PYY是否与雌二醇相互作用以调节大鼠的能量平衡和新陈代谢；以及3)阐明饮食营养对猫和牛PYY分泌的影响，并评估PYY是否与这些家畜的能量平衡有关。这些创新的研究将为PYY调节食物摄入量和体重的机制提供新的见解，从而扩大我们对肠道如何调节能量平衡的理解。重要的是，这些研究的结果可能导致开发针对伴侣动物和人类肥胖及其并发症的新治疗目标，并最终可能为优化饲料效率和提高牲畜生产力开辟新的途径。

Energy balance in animals and humans is determined by factors that coordinate energy intake with output. It is well known that obesity results from an excess of calories consumed over calories burnt. About 35% of cats and dogs are either overweight or obese. The prevalence of obesity and its complications such as diabetes are also increasing in horses and humans. Further, in the livestock industry, the efficiency with which the feed that is consumed is converted to milk and meat is a key factor determining profitability on farms. Therefore, it is important to understand the fundamental biological mechanisms regulating energy balance. After food is consumed, the gut secretes a number of peptides which in turn inform the brain to produce satiety; however, the underlying mechanisms by which the gut regulates food intake and body weight are largely unknown. The overall goal of my research program is to gain a fundamental understanding of the physiological mechanisms by which peptides secreted from the gut regulate energy balance. We have previously shown that the gut peptide - peptide YY (PYY) decreases food intake in rats. In this proposal, I will advance our understanding of the mechanisms by which PYY regulates energy balance by applying novel methods to address the following aims: 1) determine whether PYY secreted from the gut after a meal signals the brain to produce satiety, investigate how this occurs, and identify the brain regions that are involved using rat models, 2) determine whether PYY interacts with estradiol to regulate energy balance and metabolism in rats, and 3) elucidate the effects of dietary nutrients on PYY secretion in cats and cattle, and assess whether PYY is associated with energy balance in these domestic animals. These innovative studies will provide new insights into the mechanisms by which PYY regulates food intake and body weight, and thus expand our understanding of how the gut regulates energy balance. Importantly, the outcomes from these studies may lead to the development of novel therapeutic targets against obesity and its complications in companion animals and humans, and may also ultimately open up new avenues for optimizing feed efficiency and enhancing the productivity of livestock.