Regulation of Energy Balance by Dietary Protein

能量平衡是一个基本的生物过程，它依赖于作为宏量营养素消耗的能量（即卡路里）、消耗和储存的能量之间复杂的相互作用。肠道中感知和信号饮食宏量营养素的机制失调可能使宠物（猫、狗）和人类容易体重增加、肥胖和代谢并发症。重要的是，饲料效率是决定畜禽奶和肉生产盈利能力的关键因素。因此，为了制定有效的宠物和人类抗肥胖干预措施，并优化牲畜的饲料效率，了解膳食宏量营养素调节能量平衡的机制至关重要。我的研究计划的长期目标是确定肠道调节能量平衡和代谢的生理机制。我的指导假设是，饮食中蛋白质或氨基酸的过量或缺乏会通过参与外周肠-脑神经和内分泌信号机制来调节食物摄入、能量消耗和代谢。

Energy balance is a fundamental biological process that is dependent on a complex interplay of energy (i.e. calories) consumed as macronutrients, energy expended and stored. A dysregulation of the mechanisms that sense and signal dietary macronutrients in the gut may predispose pets (cats, dogs) and humans to weight gain, obesity and metabolic complications. Importantly, feed efficiency is a key determinant of profitability of milk and meat production from livestock. Thus, to develop effective anti-obesity interventions for pets and humans, and optimize feed efficiency of livestock, it is important to understand the mechanisms by which dietary macronutrients regulate energy balance. The long-term objective of my research program is to define the physiological mechanisms by which the gut regulates energy balance and metabolism. My guiding hypothesis is that an excess or deficiency of dietary protein, or amino acids, will modulate food intake, energy expenditure and metabolism by engaging peripheral gut-brain neural and endocrine signaling mechanisms. The specific short-term objectives are to: 1) Delineate the mechanisms by which high protein diets promote satiety, weight loss and improve glycemic control. We demonstrated that whey protein decreases food intake and weight gain in rat models. We will now resolve whether the vagus, hormones and microbiota are causative to whey-induced changes in energy balance, and whether exercise amplifies the metabolic benefits of protein. 2) Elucidate the mechanisms of hyperphagia and thermogenesis produced by dietary protein or amino acid restriction. We reported that low proteinhigh carbohydrate diets differentially modulate energy balance in rats. We will now unravel whether such effects persist with low proteinhigh fat diets, whether individual amino acids recapitulate the effects of protein restriction, and illuminate the underlying mechanisms of action. 3) Determine whether amino acid supplementation rescues the impaired growth performance produced by low protein diets. Little is known of the ideal combinations of synthetic amino acids that can rescue the impaired growth from low protein diets, and hence, studied here using rat and pig models. Overall, my program has significant implications for the health of pets and humans, and to the agri-food industries. Insights into the mechanisms of weight loss by protein may guide the development of novel protein based functional foods/nutraceuticals for treating obesity and diabetes in pets and humans. Notably, I will uncover key gut-brain mechanisms engaged by dietary protein to regulate energy balance. Importantly, the application of synthetic amino acids to alleviate the impaired growth of piglets on low protein diets will significantly decrease feed costs and nitrogen losses in manure, with tremendous economic and environmental implications to food animal production systems.