Regulation of Energy Balance by Dietary Protein

能量平衡是一个基本的生物过程，它依赖于作为常量营养素消耗的能量（即卡路里）、消耗和储存的能量的复杂相互作用。在肠道中感知和发出膳食常量营养素信号的机制失调可能使宠物（猫，狗）和人类易于体重增加，肥胖和代谢并发症。重要的是，饲料效率是牲畜产奶和产肉盈利能力的关键决定因素。因此，要为宠物和人类开发有效的抗肥胖干预措施，并优化牲畜的饲料效率，重要的是要了解膳食常量营养素调节能量平衡的机制。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，过量或缺乏膳食蛋白质或氨基酸，将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。 具体的短期目标是： 1)阐明高蛋白饮食促进饱腹感、减肥和改善血糖控制的机制。我们证明了乳清蛋白降低大鼠模型的食物摄入量和体重增加。我们现在将解决迷走神经，激素和微生物群是否是乳清引起的能量平衡变化的原因，以及运动是否放大了蛋白质的代谢益处。 2)阐明蛋白质或氨基酸限制引起的摄食过多和产热的机制。我们报道了低蛋白高碳水化合物饮食对大鼠能量平衡的调节作用。我们现在将阐明这种效应是否在低蛋白高脂肪饮食中持续存在，单个氨基酸是否重现了蛋白质限制的效应，并阐明了潜在的作用机制。 3)确定补充氨基酸是否能挽救低蛋白饮食造成的生长性能受损。很少有人知道合成氨基酸的理想组合，可以挽救低蛋白饮食受损的生长，因此，在这里使用大鼠和猪模型进行研究。 总的来说，我的计划对宠物和人类的健康以及农业食品行业都有重大影响。对蛋白质减肥机制的深入了解可能会指导开发新的基于蛋白质的功能性食品/营养品，用于治疗宠物和人类的肥胖和糖尿病。值得注意的是，我将揭示饮食蛋白质参与调节能量平衡的关键肠脑机制。重要的是，应用合成氨基酸来缓解低蛋白饮食仔猪生长受损将显著降低饲料成本和粪便中的氮损失，对食用动物生产系统具有巨大的经济和环境影响。

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.