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

基本信息

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
项目类别：
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

项目摘要

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，但这会导致理想的体重减轻。脂肪量、肌肉量也会减少，这对术后健康有影响。前提是在减肥后食用我们基于必需氨基酸 (EAA) 的营养配方手术将通过刺激肌肉蛋白质合成来保留肌肉质量，从而提高能量利用率。与维持肌肉质量和刺激肌肉蛋白质合成的结合相关对抗通常在减肥状态下发生的新陈代谢率下降，维持较高的体重。 EAA的能量消耗会加速体内脂肪的消耗减少，并有助于维持减肥效果。我们进一步建议，食用我们基于 EAA 的配方将减少肌肉脂质积累（在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。以下目标将测试与我们的科学前提相关的具体假设：目标 1. 使用我们专有的基于 EAA 的药物补充减肥手术后的正常饮食每天两次配方，持续 6 个月将保持肌肉质量并减少脂肪量超过在饮食中补充等氮量的乳清蛋白将直接增加肌肉质量。使用新型示踪稀释技术使用 2H3-肌酸进行测量。通过 DEXA 测量。目标 2. 肌肉蛋白分数合成率 (FSR) 和总肌肉蛋白合成率（肌肉质量 x FSR）与服用我们基于 EAA 的配方的参与者相比，其术前值的下降幅度较小乳清蛋白 FSR 将通过新型“虚拟活检”方法进行测量，该方法提供了一种两周内的综合值。目标 3. 个体的总能量消耗 (TEE) 术前率将得到更好的维持我们将在 14 天内测量基于 EAA 的配方（而不是乳清蛋白）的消耗情况。术前和术后 6 个月使用双标记水技术的间隔。目标 4. 减肥手术后六个月通过磁力测量细胞内和肌内脂质共振光谱和磁共振成像 (MRS/MRI) 将从术前开始减少与乳清蛋白相比，食用我们基于 EAA 的配方的参与者的水平更高。预计这些肌肉脂质参数的更大降低将与肌肉的更大改善有关葡萄糖稳态和肌肉蛋白质合成方面的胰岛素敏感性。这项研究的积极结果将支持我们基于 EAA 的组合物的价值，以帮助保存肌肉质量，同时促进脂肪减少并提高减肥后体重稳定的可能性外科手术。