The benefits of current pharmacological approaches to treating heart failure (HF) are near their limits and new adjunctive therapies are needed. Recent results from this PPG suggest that low carbohydrate/high fat diets may prevent the development and progression of HF. The fatty acid composition of the diet may have a major impact on development and progression of HF. Intake of polyunsaturated fatty acids (PUFA) has a more favorable effect on cardiac gene expression, mitochondrial function, and cardiomyocyte apoptosis than a high saturated fat diet. We also observed that high sugar intake may accelerate the development and progression of HF. This Project investigates the mechanistic effects of dietary macronutrient composition on the progression of HF. We hypothesize that 1) high intake of PUFA (18:2n-6 and 18:3n-3) or the EPA+DHA) prevents and reverses deterioration in mitochondrial function, apoptosis, cardiomyocyte hypertrophy, fibrosis, chamber remodeling and contractile dysfunction in HF;and 2) a high sugar diet activates insulin-stimulated growth and ROS production and accelerates the progression of HF. Studies will be performed in established models of HF. Underiying mechanisms are addressed with targeted alterations in specific pathways using nutritional, pharmacological, and genetic approaches.
The specific aims are: 1) Assess the ability of high fat diets comprised of saturated fatty acids or PUFA to stop or reverse the progression of HF compared to a standard high carbohydrate diet. 2) Determine the effects of dietary supplementation of a standard high carbohydrate diet with UJ-3PUFA (EPA+DHA) on the progression of established HF. 3) Elucidate the role of insulin signaling in the adverse effects of a high sugar diet in HF. 4) Determine the role of ROS generation in mediating the adverse effects of high sugar diet in HF.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
7P01HL074237-10
Application #
8532017
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$265,463
Indirect Cost
$28,834
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
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