Relative Sarcopenia and Cardiometabolic Risk in Young Adults with Obesity

项目摘要/摘要 肥胖是众所周知的心脏代谢性疾病的危险因素，也是日益严重的公共健康问题。然而，几乎没有 已知肌肉质量和质量对心脏代谢风险的影响，包括2型糖尿病(DM)， 特别是在超重/肥胖的年轻人中。拟议中的研究具有确定目标的潜力 用于预防和治疗这一公共卫生问题。 中心假设是相对肌质疏松症(即相对于BMI的低肌肉质量)和受损的肌肉 随着时间的推移，质量(即心肌细胞内脂质(IMCL)和线粒体功能障碍)会导致更高的DM风险 对于超重/肥胖的年轻人。我们还假设，常见的基因变异与 胰岛素抵抗，以及肥胖相关的相关激素缺乏，都会导致相对的骨质疏松症 并损害肌肉质量，导致更高的糖尿病风险。 这位候选人是哈佛医学院的医学讲师，也是 马萨诸塞州综合医院(MGH)，非常有资格并坚定地致力于开发 独立调查员的职业生涯。她的短期目标是发展技能并获得初步的 向她的第一个R级独立NIH资助研究过渡所需的数据。她长长的- 学期目标是成为一名独立的、以患者为中心的研究人员，利用遗传流行病学、内分泌 生理学和复杂的成像技术，以阐明可能有助于增加 超重/肥胖年轻人的心脏代谢风险，并确定两者的潜在靶点 预防和治疗。她有着出色的成功记录，包括获奖、飞行员赠款和 出版，并由专家和高度投资的指导团队支持， 美国国立卫生研究院支持的神经内分泌学、放射学、流行病学和遗传学的临床研究人员 流行病学。她和她的导师设计了一个有针对性的培训计划，包括共同指导和 说教节目。 麻省理工学院和哈佛医学院的制度环境很好，拥有多种资源 可从MGH医学部、MGH临床研究部和哈佛大学 临床和翻译科学中心，所有这些都提供了无数的教学机会，设施和 对候选人的支持。神经内分泌科和医学部已经做出了强有力的 对候选人的承诺，包括90%受保护的时间、空间、学习协调员支持和一名教师 任命，目的是促进候选人作为独立调查员的职业生涯。

PROJECT SUMMARY/ABSTRACT Obesity is a well-known cardiometabolic disease risk factor and growing public health problem. However, little is known about the impact of muscle mass and quality on cardiometabolic risk, including type 2 diabetes (DM), especially in young adults with overweight/obesity. The proposed research has the potential to identify targets for the prevention and treatment of this public health problem. The central hypothesis is that relative sarcopenia (i.e. low muscle mass relative to BMI) and impaired muscle quality (i.e. intramyocellular lipid (IMCL) and mitochondrial dysfunction) contribute to higher DM risk over time in young adults with overweight/obesity. We also hypothesize that common genetic variants associated with insulin resistance, as well as obesity-related relative hormone deficiencies, contribute to relative sarcopenia and impaired muscle quality and lead to higher DM risk. The candidate is an Instructor of Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital (MGH) who is highly qualified for and deeply committed to developing a career as an independent investigator. Her short-term goal is to develop the skills and obtain the preliminary data necessary to make the transition to her first R-level independent NIH grant-supported research. Her long- term goal is to become an independent patient-oriented researcher leveraging genetic epidemiology, endocrine physiology and sophisticated imaging techniques to elucidate mechanisms that may contribute to increased cardiometabolic risk in young adults with overweight/obesity, and to identify potential targets for both prevention and treatment. She has an outstanding track record of success, including awards, pilot grants and publications, and is supported by an expert and highly invested mentorship team composed of successful, NIH-supported clinical investigators in Neuroendocrinology, Radiology, Epidemiology and Genetic Epidemiology. She and her mentors have designed a targeted training plan consisting of co-mentorship and a didactic program. The institutional environment is outstanding at MGH and Harvard Medical School, with multiple resources available from the MGH Department of Medicine, the MGH Division of Clinical Research, and the Harvard Clinical and Translational Science Center, all of which offer a myriad of didactic opportunities, facilities and support to the candidate. The Neuroendocrine Unit and Department of Medicine have made a strong commitment to the candidate, including 90% protected time, space, study coordinator support and a faculty appointment, with the goal of fostering the candidate's career as an independent investigator.