The New York Obesity Nutrition Research Center

Letter Of Intent

LETTERHEAD

To: Xavier Pi-Sunyer, M.D.
Director for Pilot &Feasibility Programs
New York Obesity Nutrition Research Center
c/o Katherine Marquez, katmarquez@chpnet.org 

Dear Dr. Pi-Sunyer,

This letter serves as notice of my intent to apply for a NYONRC Pilot & Feasibility Grant on XXXX, 20XX. I am an investigator in the field of diabetes and obesity and I am proposing an innovative/high risk project.

More than 50% of African American women in the US are obese (BMI>30) and African Americans have a higher prevalence type 2 diabetes mellitus (T2DM) than Caucasians. We have recently demonstrated metabolic inflexibility in lean and obese healthy premenopausal African American women compared to Caucasian counterparts (Berk,JCEM, 2006). The main feature of metabolic inflexibility is the inability to increase fat oxidation in response to increased fat availability. These differences were not explained by differences in substrate or hormone levels. Impaired substrate switching has also been described in first degree relatives of T2DM patients; there is evidence that, in these populations, metabolic inflexibility relates to mitochondrial dysfunction (Ukropcova, Diabetes, 2007).

Our overall hypothesis is that the observed differences in substrate utilization between healthy African American and Caucasians women are a result of differences in mitochondrial function. Specifically for this project we propose to determine whether naturally-occurring variants in mitochondrial genome in the groups of women we have studied (mtDNA polymorphism, haplogroups) relate to the phenotypical features described (inability to increase fat oxidation in response to an increase in fat availability i.e. high fat diet). The project involves DNA collection and mtDNA haplotyping on microchips for all the subjects who had undergone phenotypical studies so far. In addition to utilization of the DERC labs we will collaborate with Columbia mitochondrial genetics experts Drs. S. Zanssen and E. Schon who have expressed enthusiasm for such a project. A positive outcome of our study may have extensive implications for mechanistic studies of substrate utilization alterations in obesity and T2DM.

Thank you very much for your consideration,

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