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代餐饮料，该饮料最终将在肥胖老年人的热量限制减肥（CRWL）期间保持肌肉损失。我们之前开发了一种富含必需氨基酸（TMR）的专利混合物的代餐，其在刺激老年人肌肉蛋白质合成（MPS）方面的有效性是乳清蛋白的三倍以上。利用该TMR和基于最低蛋白质需求（0.8 gm蛋白质/kg/天）的蛋白质摄入量，我们证明了与竞争性代餐相比脂肪组织的更大减少。即便如此，志愿者仍然失去了一些肌肉质量使用TMR。这可能反映了老年人的最佳蛋白质摄入量明显大于0.8 g/kg/天，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EAA的绝对量，还包括瓜氨酸，以进一步促进骨骼肌对EAA的利用。尽管MyoEon已充分开发用于测试本项目的中心假设，但本第1阶段项目的一部分将进一步优化产品的几个方面。该提案的首要假设是，与市售“高蛋白”代餐（Bariatric Advantage）相比，MyoEon的摄入将通过增加蛋白质合成速率和降低蛋白质分解速率来促进净蛋白质合成的改善。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可以在零售市场上盈利的假设。我们将直接与我们的食品科学合作伙伴（Mattson，Inc.，Foster City，CA; http：//www.foodcom.com/），以确立MyoEon制剂的验收标准。将通过确定MyoEon作为用于减肥的可口（由焦点小组确定）和具有成本效益（每个产品的总成本低于1.00美元）的产品的可行性来定义成功指标。具体目标二：我们将证明与Bariatric Advantage相比，MyoEon在CRWL期间通过增加净蛋白质合成（计算为通过稳定同位素示踪剂方法确定的蛋白质合成和分解之间的差异）来保持瘦体重的可行性。证明MyoEon上级最高质量的竞争对手将代表这一目标的成功指标，并作为与Mountain West临床转化研究-基础设施网络联合进行的II期随机临床试验（RCT）的机制基础。在本RCT中，我们将在一项结局研究中确定MyoEon与Bariatric Advantage的有效性，该研究重点关注肌肉质量的维持和功能能力的改善，以及体重减轻的代谢益处的放大。

 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.