Muscle preservation during weight loss in older, overweight individuals

 描述(由申请人提供)：该项目的总体目标是测试一种膳食替代饮料，该饮料最终将在卡路里限制减肥(CRWL)期间保持肥胖老年人的肌肉损失。我们之前开发了一种富含必需氨基酸(TMR)专利混合物的膳食替代品，在刺激老年人肌肉蛋白质合成(MPS)方面的效率是乳清蛋白的三倍多。利用这种TMR和基于最低蛋白质需要量(0.8克蛋白质/公斤/天)的蛋白质摄入量，我们证明了与竞争性膳食替代品相比，脂肪组织的减少更多。即便如此，使用TMR的志愿者仍然减少了一些肌肉质量。这可能反映了这样一个事实，即老年人的最佳蛋白质摄入量显著高于0.8g/kg/天，而CRWL的低热量条件进一步提高了对最佳蛋白质的需求。在我们的配方(MyoEon)中，我们现在增加了EaAs的绝对量，还包括瓜氨酸，以进一步促进EaAs对骨骼肌的利用。虽然MyoEon已经开发得足够好，可以测试这个项目的中心假设，但这个第一阶段项目的一部分将进一步优化产品的几个方面。这项建议的主要假设是，与商业上可获得的“高蛋白”膳食替代品相比，摄入MyoEon将通过增加蛋白质合成速度和降低蛋白质分解率来促进蛋白质净合成的改善(减肥优势)。具体目标1：我们将优化配料、生产、包装和履行的适口性和成本，这将验证MyoEon可以在零售市场上有利可图销售的假设。我们将直接与我们的食品科学合作伙伴(马特森公司，加利福尼亚州福斯特城；http://www.foodcom.com/))合作，建立MyoEon配方的接受标准。成功的标准将通过确定MyoEon作为一种可口的(由重点小组确定的)和成本效益(每种产品的总成本低于1.00美元)用于减肥的产品的可行性来定义。具体目标2：我们将通过增加蛋白质净合成来证明MyoEon在CRWL期间保持瘦体重的可行性，与减肥优势相比，净蛋白质合成是通过稳定同位素示踪方法确定的蛋白质合成和分解之间的差异来计算的。证明MyoEon优于最高质量的竞争对手将代表着实现这一目标的成功标准，并将作为与西部山区临床转化研究基础网络联合进行的第二阶段随机临床试验(RCT)的机械基础。在这项随机对照试验中，我们将在一项结果研究中确定MyoEon与减肥优势的有效性，这项研究的重点是维持肌肉质量和改善功能能力，以及扩大减肥的代谢益处。

 DESCRIPTION (provided by applicant): The overall goal of this project is to test a meal replacement beverage that will ultimately preserve muscle loss during calorie restriction weight loss (CRWL) in obese older individuals. We previously developed a meal replacement rich with a proprietary blend of essential amino acids (TMR) that was more than three times as effective as whey protein in stimulating muscle protein synthesis (MPS) in the elderly. Utilizing this TMR and protein intake based on minimal protein requirements (0.8 gm protein/kg/day), we demonstrated a greater reduction in adipose tissue compared to a competitive meal replacement. Even so, volunteers still lost some muscle mass using the TMR. This likely reflected the fact that the optimal protein intake in older individuals is significantly greater thn 0.8 g/kg/day, and the hypocaloric condition of CRWL further elevated the need for optimal protein. In our formulation (MyoEon), we have now increased the absolute amount of EAAs and also included citrulline to even further promote the availability of EAAs to skeletal muscle. Although MyoEon is sufficiently developed for testing the central hypothesis of this project, part of this Phase 1 project will be to further optimize several aspects of product. The overarching hypothesis of this proposal is that the ingestion of MyoEon will foster an improvement in net protein synthesis, through an increased rate of protein synthesis and a decreased rate of protein breakdown as compared to a commercially available "high protein" meal replacement (Bariatric Advantage). Specific Aim 1: We will optimize the palatability and cost for ingredients, production, packaging, and fulfillment, which will validate the hypothesis that MyoEon can be profitably sold in retail markets. We will work directly with our food science partner (Mattson, Inc., Foster City, CA; http://www.foodcom.com/) to establish the criteria of acceptance for the formulation of MyoEon. The metric of success will be defined by establishing the feasibility of MyoEon as a palatable (determined by focus groups) and cost effective (total costs per product less than $1.00) product for use in weight loss. Specific Aim 2: We will demonstrate the feasibility of MyoEon to preserve lean body mass during CRWL as compared to Bariatric Advantage, through increased net protein synthesis, calculated as the difference between protein synthesis and breakdown determined by stable isotope tracer methodology. Demonstration that MyoEon is superior to the highest quality competitor will represent the metric of success for this aim and serve as the mechanistic underpinning for a Phase II randomized, clinical trial (RCT) performed in conjunction with the Mountain West Clinical Translational Research - Infrastructure Network. In this RCT, we will establish the effectiveness of MyoEon vs Bariatric Advantage in an outcome study focused on maintenance of muscle mass and improvement of functional capacity, as well as amplification of the metabolic benefits of weight loss.