Nutritional Stimulation of Muscle Protein Synthesis and Metabolic Rate After Bariatric Surgery

减肥手术后肌肉蛋白质合成和代谢率的营养刺激

• 批准号: 10005845
• 负责人: ROBERT R WOLFE
• 金额: $ 80.65万
• 依托单位: AMINO COMPANY LLC, THE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005845
• 关键词: Base Composition; Body Composition; Body Weight decreased; Body fat; Calories; Consumption; Creatine; Data; Diet; Dietary Supplementation; Dilution Techniques; Dual-Energy X-Ray Absorptiometry; Energy Intake; Energy Metabolism; Essential Amino Acids; Fatty acid glycerol esters; Food; Formulation; Health Benefit; Individual; Industry; Intramuscular; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Measurement; Measures; Metabolic; Methods; Modeling; Morbid Obesity; Muscle; Muscle Proteins; Muscular Atrophy; Nutritional; Obesity; Operative Surgical Procedures; Participant; Protein Biosynthesis; Proteins; Source; Supplementation; Techniques; Testing; Time; Tracer; Translating; United States; Weight; Whey Protein; bariatric surgery; base; blood glucose regulation; common treatment; dosage; doubly-labeled water; effective therapy; improved; insulin sensitivity; lean body mass; metabolic rate; muscle form; novel; preservation; protein metabolism; spectroscopic imaging; total energy expenditure; virtual biopsy; weight loss program

7. Project Summary/Abstract Bariatric surgery has become a common treatment for severe obesity. While this results in the desired loss of fat mass, muscle mass is also lost with implications for post-surgical health benefits. It is our overarching premise that consumption of our essential amino acid (EAA)-based nutritional formulation following bariatric surgery will preserve muscle mass by stimulating muscle protein synthesis. As a result, the energy utilization associated with the combination of maintained muscle mass and stimulated muscle protein synthesis will counter the decrease in metabolic rate that normally occurs in a weight-reduced state. Maintenance of a higher energy expenditure by EAA consumption will accelerate loss of body fat, as well as help maintain weight loss. We further propose that consumption of our EAA-based formulation will reduce muscle lipid accumulation (in the form of both intramyocelluar lipids and intramuscular fat), which will translate to greater improvements in glucose homeostasis and muscle protein metabolism. The following aims will test specific hypotheses related to our scientific premise: Aim 1. Supplementation of the normal diet following bariatric surgery with our proprietary EAA-based formulation twice per day for 6 months will maintain muscle mass and reduce fat mass more than supplementation of the diet with an isonitrogenous amount of whey protein. Muscle mass will be directly measured using a novel tracer-dilution technique using 2H3-creatine. Fat mass and lean body mass will be measured by DEXA. Aim 2. Muscle protein fractional synthetic rate (FSR) and total muscle protein synthesis (muscle mass x FSR) will decline less from pre-surgery values in participants consuming our EAA-based formulation as compared to whey protein. Muscle protein FSR will be measured by the novel “virtual biopsy” method, which provides an integrated value over two weeks. Aim 3. The pre-surgery rate of total energy expenditure (TEE) will be better maintained in individuals consuming our EAA-based formulation as opposed to whey protein. TEE will be measured over 14-day intervals using the doubly-labeled water technique before and 6-months following surgery. Aim 4. Six months after bariatric surgery both intracellular and intramuscular lipids measured by magnetic resonance spectroscopy and magnetic resonance imaging (MRS/MRI) will be reduced from the pre-surgery levels to a greater extent in participants consuming our EAA-based formulation than whey protein. We anticipate that a greater reduction in these muscle lipid parameters will be related to greater improvement in insulin sensitivity in terms of glucose homeostasis and also in terms of muscle protein synthesis. Positive results of this study will support the value of our EAA-based composition to aid in preservation of muscle mass while facilitating fat loss and improving the likelihood of weight stabilization following bariatric surgery.

7.项目总结/摘要 减肥手术已成为严重肥胖症的常见治疗方法。虽然这导致期望的 脂肪量、肌肉量也会损失，这意味着手术后的健康益处。这是我们的首要任务 前提是在减肥后消耗我们的基于必需氨基酸（EAA）的营养制剂 手术将通过刺激肌肉蛋白质合成来保留肌肉质量。因此，能源利用率 与维持的肌肉质量和刺激的肌肉蛋白质合成的组合相关联， 对抗通常在减肥状态下发生的代谢率下降。维持较高的 EAA消耗的能量消耗将加速身体脂肪的损失，以及帮助保持体重减轻。 我们进一步提出，我们的EAA基制剂的消耗将减少肌肉脂质积累（在2000年）。 肌细胞内脂质和肌内脂肪的形式），这将转化为更大的改善， 葡萄糖稳态和肌肉蛋白质代谢。 以下目标将检验与我们的科学前提相关的具体假设： 目标1。在减肥手术后用我们专有的基于EAA的 每天两次，持续6个月， 在饮食中补充等氮量的乳清蛋白。肌肉质量将直接 使用2 H3-肌酸的新型示踪稀释技术测量。脂肪量和瘦体重 通过DEXA测量。 目标2.肌肉蛋白合成率（FSR）和总肌肉蛋白合成（肌肉质量x FSR） 与使用我们的EAA制剂的受试者相比， 乳清蛋白肌肉蛋白FSR将通过新的“虚拟活检”方法进行测量，该方法提供了一种 综合价值超过两周。 目标3.术前总能量消耗率（TEE）将在个体中得到更好的维持 食用我们的EAA为基础的配方，而不是乳清蛋白。将在14天内测量TEE 在术前和术后6个月使用双标记水技术。 目标4。减肥手术后6个月，通过磁共振成像测量细胞内和肌内脂质 将减少术前的共振波谱和磁共振成像（MRS/MRI） 与乳清蛋白相比，在食用我们的EAA配方的参与者中，我们 预期这些肌肉脂质参数的更大降低将与以下方面的更大改善相关： 在葡萄糖稳态方面以及在肌肉蛋白质合成方面的胰岛素敏感性。 本研究的积极结果将支持我们的基于EAA的组合物的价值，以帮助保存 肌肉质量，同时促进脂肪减少和改善减肥后体重稳定的可能性 手术