Role of Gut Peptides in the Regulation of Energy Balance

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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.