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Acute High Fat Mediated Cardioprotection and the Underlying Mechanisms of Action

Haar, Lauren
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901036

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Systems Biology and Physiology.
Abstract Background and Significance: Evidence from large-scale clinical studies shows a paradoxical relationship between a high fat diet and myocardial pathophysiology. Termed the `obesity paradox’, data from these studies indicate that obesity and a high BMI have an inverse relationship with mortality after myocardial infarction (MI), even with increased risk for an initial coronary event. Chronically, high fat diets lead to dyslipidemia, obesity-induced inflammation, adipogenesis, glucose resistance, diabetes, and sustained elevation of serum cholesterol levels. This work will investigate the discovery that cardioprotection against ischemia/reperfusion (I/R) injury occurs after a very short duration of high fat feeding. This timeline suggests that this cardioprotection is independent from the chronic effects of high fat feeding. Rather, there must be an acute effect, the nature of which has not previously been studied. Objectives: These studies investigated the effects of the high fat diet on infarct size post-MI, on NF-?B activation in the heart, and the potential mechanistic relationship between NF-?B and high fat diet (HFD) induced cardioprotection. We hypothesize that NF-?B is activated acutely in the heart via high fat diet, and contributes to the regulation of a cardioprotective gene network. NF-?B is known to be activated in inflammatory states and also is activated by specific oxidized lipids in tissues. NF-?B has been shown to play a pro-cell death role in I/R as well as a protective role in ischemic preconditioning. Thus, it is a likely mediator of the effects of a high fat diet on cardiac myocyte signaling. Understanding this mechanism is essential to revealing new therapeutic targets (genes and their products) that can be manipulated to utilize cardioprotection in the clinical setting. Major Findings: The primary finding of this study shows that short-term high fat diet elicits a cardioprotective effect against I/R injury. This effect is attenuated with long term high fat feeding. Since short term feeding does not present complications commonly found in chronic high fat studies it presents a promising option for development into clinical therapy. High fat mediated protection is predicated on the activation of NF-?B gene programs that contribute to the upregulation of autophagy. This is commonly observed in cardioprotective preconditioning phenomena. The activation of these gene programs may be facilitated by neural-hormonal activation of cell receptors via adiponectin, influential changes in intestinal microflora and activation of serum-mediated events. Conclusions: Acute high fat feeding is cardioprotective against I/R injury. A regulatory checkpoint in this effect occurs at the level of NF-?B transcription. High fat feeding regulates activation of NF-?B profiles known to play a role in cardioprotection, including HSP70.3 and Beclin-1. The induction of autophagic programs without subsequent increase in apoptosis also contributes to this effect. This activation is hypothesized to be due, in part, to the action of adiponectin mediated signaling in the myocardium.
Walter Jones, Ph.D. (Committee Chair)
Jack Rubinstein, M.D. (Committee Member)
Hamid Eghbalnia, Ph.D. (Committee Member)
Nelson Horseman, Ph.D. (Committee Member)
John Lorenz, Ph.D. (Committee Member)
Patrick P.W. Tso, Ph.D. (Committee Member)
158 p.
Physiological Psychology
high fat diet; ischemia reperfusion injury; cardioprotection; NF kappaB

Recommended Citations

Citations

  • Haar, L. (2014). Acute High Fat Mediated Cardioprotection and the Underlying Mechanisms of Action [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901036

    APA Style (7th edition)

  • Haar, Lauren. Acute High Fat Mediated Cardioprotection and the Underlying Mechanisms of Action. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901036.

    MLA Style (8th edition)

  • Haar, Lauren. "Acute High Fat Mediated Cardioprotection and the Underlying Mechanisms of Action." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901036

    Chicago Manual of Style (17th edition)

ucin1406901036
462
© 2014, some rights reserved.Creative Commons License Acute High Fat Mediated Cardioprotection and the Underlying Mechanisms of Action by Lauren Haar is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.