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The Role of Dietary Fat and Carbohydrate in Cardiac Hypertrophy and Failure

Chess, David J.
http://rave.ohiolink.edu/etdc/view?acc_num=case1224770615

Abstract Details

2009, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
Despite advanced diagnostic techniques, heart failure (HF) remains a clinical, societal, and economic burden. Pharmacological treatments effectively manage HF but increase medical care cost by prolonging survival without improving prognosis. Thus, novel therapies that act independently of medicinal targets are needed to prevent or slow the progression of HF. Diet, a major component of daily life, is a potential strategy to impact HF pathogenesis. Thus, the overall goal of this dissertation was to assess the direct effects of dietary macronutrients on the myocardium during pathological cardiac hypertrophy and failure. The main objectives were (i) to assess the effects of carbohydrate composition on the development of hypertrophy and contractile dysfunction and (ii) compare high carbohydrate/low fat diets with low carbohydrate/high fat diets on HF pathogenesis. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload in mice. In the first series of studies, mice were subjected to aortic banding or sham surgery and placed on either a control, high starch, or high fructose diet for 16 weeks. Animals on the high fructose diet exhibited increased mortality, left ventricular (LV) hypertrophy and remodeling, systolic dysfunction, impaired mitochondrial enzyme activities, and dramatic upregulation of myosin heavy chain β (MHCβ) compared to starch-fed mice. Treatment with the antioxidant tempol attenuated the deleterious effects of fructose, consistent with the idea that high sugar diets increase myocardial oxidative stress. Evidence of a role for insulin signaling in the adverse effects of fructose was inconclusive, as addressed in cardiac insulin receptor knockout (CIRKO) mice. The second series of studies compared high fat to high carbohydrate diets on the hypertrophic response. Following both short- and long-term dietary treatment, fat-fed animals had comparable hypertrophy and dysfunction compared to high carbohydrate-fed mice. Associated with high fat feeding was preserved mitochondrial enzyme activities, suggesting that increased fat consumption may preserve mitochondrial function and normal cardiac energetics. These findings suggest that dietary macronutrient composition can have a major impact on HF development and progression. The pleiotropic actions of diet, in conjunction with targeted drug therapies, may suppress the incidence and slow the progression of chronic disease.
William Stanley, PhD (Advisor)
Thomas Nosek, PhD (Committee Chair)
Margaret Chandler, PhD (Committee Member)
Thomas Egelhoff, PhD (Committee Member)
Paul Ernsberger, PhD (Committee Member)
Brian Hoit, MD (Committee Member)
Ulrich Hopfer, MD, PhD (Committee Member)
214 p.
TAC; sham; Diet; FAT; Fructose; HYPERTROPHY; Starch

Recommended Citations

Citations

  • Chess, D. J. (2009). The Role of Dietary Fat and Carbohydrate in Cardiac Hypertrophy and Failure [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1224770615

    APA Style (7th edition)

  • Chess, David. The Role of Dietary Fat and Carbohydrate in Cardiac Hypertrophy and Failure. 2009. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1224770615.

    MLA Style (8th edition)

  • Chess, David. "The Role of Dietary Fat and Carbohydrate in Cardiac Hypertrophy and Failure." Doctoral dissertation, Case Western Reserve University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1224770615

    Chicago Manual of Style (17th edition)

case1224770615
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© 2008, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.