Obesity is a major public health problem affecting over one third of adults in the United States and one in five children. Obesity is related to an increased risk of cardiovascular mortality, which may in part be mediated through a direct effect on the heart leading to dysfunction. However, the time course over which obesity leads to cardiac dysfuncfion, the underlying mechanisms of myocardial dysfunction in obesity, and potential treatments have not been fully elucidated. Our preliminary data ufilizing cardiac magnefic resonance imaging (MRI) show abnormalifies in the magnitude of contracfion, synchrony of contraction, and myocardial mass in the hearts of mice fed a high-fat Western diet. The objective of this project is to define the time course over which this dysfunction occurs in mice, evaluate the role of hypertension in the development of this dysfunction, and to translate this work into humans by determining whether children in our pediatric obesity clinic have evidence of cardiac dysfunction. This project has 3 specific aims as follows: 1) Determine the time course over which myocardial dysfunction develops in mice fed a high-fat Western diet. We will quantify advanced measures of cardiac function assessing mass, contraction and relaxation and synchrony overtime in a longitudinal study using magnetic resonance imaging. 2) Determine the effect of anti-hypertensive therapy on the development of hypertrophy and cardiac dysfunction in mice fed a high-fat Western diet. Mice on a high-fat Western diet develop obesity-related hypertension that is reversible with anti-hypertensive therapy. However, the effect of anti-hypertensive therapy on cardiac function in obese mice has not been studied and may elucidate underiying mechanisms. We will compare cardiac function measured in the'mice on a high-fat Western diet in specific aim 1 to a group of mice on a high-fat Western diet and hydralazine. 3) Quantify cardiac function in children with obesity using advanced MRI. State-of-the-art technology at the University of Kentucky enables us to directly translate our findings in mice into our pediatric obesity clinic with over 800 patients. The effect of obesity on myocardial function in children is largely unknown.

Public Health Relevance

Obesity affects over one third of adults in the United States and one in five children. The objective of this project is to understand the effects of obesity on the function of the heart using advanced magnetic resonance imaging (MRI) of the hearts of both mice and humans. Part of this project will also investigate the specific role of blood pressure medications on helping to protect the heart from the effects of obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103527-07
Application #
8733724
Study Section
Special Emphasis Panel (ZGM1-TWD-Y)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
7
Fiscal Year
2014
Total Cost
$270,067
Indirect Cost
$90,068
Name
University of Kentucky
Department
Type
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
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