Letter Of Intent
LETTERHEAD
To: Xavier Pi-Sunyer, M.D.
Director for Pilot &Feasibility Programs
New York Obesity Nutrition Research Center
c/o Cherie Ilse, cilse@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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