In 1954 Vague identified central adiposity as a key determinant of several common chronic diseases including diabetes, myocardial infarction, hypertension and stroke. Vague contrasted the 'apple' pattern with metabolically beneficial gluteal - femoral adipose tissue (pears). This observation spawned more than a half century of clinical and laboratory investigation yet, there is still a major gap in our knowledge regarding th molecular underpinnings of adipose tissue patterning. It is clear that the relationship between adiposity and cardiovascular and diabetes disease risk is tightly related to fat patterning (apple vs. pear). In this regard, obese women who have a preponderance of abdominal subcutaneous fat (apple-shaped) have a higher risk of developing insulin resistance, diabetes and CVD relative to women who carry their excess weight in gluteal/thigh adipose tissue (pear-shaped). This proposal addresses the fundamental mechanisms associated with depot specific adipose function directly in humans. Our preliminary published and new unpublished studies support the hypothesis that fat depot specific gene expression and associated epigenetic signatures are maintained when abdominal vs. gluteal pre-adipocytes are cultured in vitro. The proposed new experiments will extend these studies to reveal genome-wide differences in epigenetic marks in adipose tissue and adipocytes from both men and women. We will also investigate the different gene expression patterns and associated epigenetic marks that define the pear vs. apple body type of the American adult female. We will uncover new fundamental molecular signatures and processes that are relevant to development of insulin resistance, diabetes and cardiovascular disease.

Public Health Relevance

Our preliminary published and new unpublished studies support the hypothesis that fat depot specific gene expression and associated epigenetic signatures are maintained when abdominal vs. gluteal pre-adipocytes are cultured in vitro. The proposed new experiments will extend these studies to reveal genome-wide differences in epigenetic marks in adipose tissue and adipocytes. We hypothesize that these epigenetic marks are important to understanding several common chronic diseases such as diabetes and cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK107009-02
Application #
9306064
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Blondel, Olivier
Project Start
2016-06-28
Project End
2020-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Florida Hospital
Department
Type
DUNS #
824843312
City
Orlando
State
FL
Country
United States
Zip Code
32803
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