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费的能量(即卡路里)、消耗和储存的能量的复杂相互作用。肠道中感知和传递膳食中大量营养素的机制的失调可能会使宠物(猫、狗)和人类容易出现体重增加、肥胖和代谢并发症。重要的是，饲料效率是牲畜生产牛奶和肉类的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减肥干预措施，并优化牲畜的饲料效率，了解膳食中大量营养素调节能量平衡的机制是很重要的。我的研究计划的长期目标是确定肠道调节能量平衡和新陈代谢的生理机制。我的指导性假设是，饮食蛋白质或氨基酸的过量或不足，将通过参与外周肠脑神经和内分泌信号机制来调节食物的摄入量、能量消耗和新陈代谢。 具体的短期目标是： 1)描述高蛋白饮食促进饱腹感、体重减轻和改善血糖控制的机制。我们在大鼠模型中证明了乳清蛋白减少了食物摄入量和体重增加。我们现在将解决迷走神经、激素和微生物区系是否导致乳清诱导的能量平衡变化，以及运动是否放大蛋白质的新陈代谢益处。 2)阐明限制蛋白质或氨基酸摄入引起的巨噬和发热的机制。我们报道了低蛋白、高碳水化合物饮食对大鼠能量平衡的不同调节作用。我们现在将揭示这种影响是否在低蛋白高脂肪饮食中持续存在，单个氨基酸是否概括了蛋白质限制的影响，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质日粮所致的生长性能受损。很少有人知道合成氨基酸的理想组合可以从低蛋白质饮食中挽救受损的生长，因此，在这里使用大鼠和猪的模型进行研究。 总体而言，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。对蛋白质减肥机理的洞察可能会指导基于蛋白质的新型功能食品/营养食品的开发，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道-大脑机制。重要的是，应用合成氨基酸来缓解低蛋白质日粮下仔猪的生长障碍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.