NAD+ and metabolic flexibility

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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.