NAD+ and metabolic flexibility

摘要 在这个再进入补充概述的研究是为了准备候选人，博士。 Markan拥有成为脂肪组织专家所需的技术和知识专长， 衰老、NAD+生物学和代谢。具体来说，Markan博士将在体内和体外代谢 除了分析肥胖症患者的皮下脂肪活检外，还进行了脂肪的表型研究。 脂肪NAD+生物学和脂肪衰老与代谢疾病及其生物学有关 作为治疗代谢性疾病的潜在手段正在被积极研究。基于这个前提，博士。 Markan的工作将提供有关可用于治疗人类肥胖的过程的见解。的 提出了以下三个研究：1）确定NAMPT表达的缺失是否驱动了发育 2）确定白色和棕色脂肪细胞中NAMPT表达的增加是否与白色和棕色脂肪细胞中NAMPT表达的增加有关。 棕色脂肪细胞足以防止脂肪细胞衰老的诱导; 3）确定NMN是否 补充可以逆转从肥胖和前驱糖尿病患者获得的脂肪组织的衰老。 此补充申请旨在允许Markan博士将其工作完全过渡到 在两年的奖励期结束时独立。概述的研究将由Markan博士进行 她的指导团队由Klein博士、Finck博士和Abumrad博士组成。马肯医生将 通过与她的指导团队定期和直接的互动来支持她。通过这一重新进入补充， 博士Markan将扩大她的技术和科学知识基础，获得新的技能，并生成数据， 使她成为一名独立的学术科学家。华盛顿医学系 大学，老年医学和营养科学部，以及克莱因博士，芬克博士和 Abumrad将为开展拟议的研究提供丰富的环境，并深深致力于博士。 马克的成功

ABSTRACT The studies outlined in this Re-Entry Supplement are designed to prepare the candidate, Dr. Kathleen Markan, with the technical and intellectual expertise required to become an expert in adipose tissue senescence, NAD+ biology, and metabolism. Specifically, Dr. Markan will perform in vivo and in vitro metabolic phenotyping studies of adipose in addition to analyzing subcutaneous adipose biopsies of people with obesity. Adipose NAD+ biology and adipose senescence have been implicated with metabolic disease and their biology is being actively studied as a potential means for treating metabolic disease. Based on this premise, Dr. Markan's work will provide insight regarding processes that could be used to treat human obesity. The following three studies are proposed: 1) determine whether loss of NAMPT expression drives the development of senescence in white and brown adipocytes; 2) define whether increased NAMPT expression in white and brown adipocytes is sufficient to prevent the induction of adipocyte senescence; 3) determine whether NMN supplementation can reverse senescence in adipose tissue obtained from people with obesity and prediabetes. This Supplement application was designed to allow Dr. Markan to transition her work to full independence at the end of the two-year award period. The outlined studies will be conducted by Dr. Markan with guidance from her mentoring team consisting of Drs. Klein, Finck, and Abumrad. Dr. Markan will be supported through regular and direct interactions with her mentoring team. Through this Re-Entry Supplement, Dr. Markan will expand her technical and scientific knowledge base, acquire new skills and generate data that will lead to her success as an independent academic scientist. The Department of Medicine at Washington University, the Division of Geriatrics and Nutritional Sciences, and the mentoring team of Drs. Klein, Finck, and Abumrad will provide a rich environment for conducting the proposed studies and are deeply committed to Dr. Markan's success.