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Effects of High Saturated Fat on Myocardial Contractile and Mitochondrial Function in Heart Failure
Rennison, Julie Helene

2008, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.

Lipid accumulation in non-adipose tissue may play a role in the pathophysiology of heart failure. Accumulation of myocardial lipids and ceramide is associated with decreased contractile function, mitochondrial oxidative phosphorylation, and electron transport chain (ETC) complex activities. We hypothesized that the progression of heart failure would be exacerbated by elevated myocardial lipids and a ceramide-induced inhibition of oxidative phosphorylation and ETC activities. Rats were fed a normal (14% kcal fat) or high fat diet (60% kcal fat) for two weeks. Heart failure was induced by coronary artery ligation. High fat feeding prior to ligation surgery increased surgical mortality, consequently the study was modified so that all rats remained on the normal diet prior to ligation surgery. Following ligation surgery, rats were fed a normal (HF) or high fat diet (HF+FAT) for eight weeks. Sham-operated animals were fed a normal diet. State 3 respiration and ETC complex activities were increased in subsarcolemmal mitochondria (SSM) of HF+FAT, despite elevated myocardial ceramide. No further progression of left ventricular dysfunction was evident in HF+FAT.

We then investigated possible mechanisms by which high fat improved mitochondrial function in heart failure. We hypothesized that a high fat diet during heart failure would increase mitochondrial fatty acid oxidation and state 3 respiration by activating genes involved in fatty acid uptake and utilization. Rats underwent ligation or sham surgery and were fed a normal (SHAM, HF) or high fat diet (SHAM+FAT, HF+FAT) for eight weeks. State 3 respiration using lipid substrates was elevated in SSM of HF+FAT and correlated to increased activities of short-, medium- and long-chain acyl-CoA dehydrogenase. This was associated with improved myocardial contractility as assessed by LV +dP/dt max. Despite decreased medium-chain acyl-CoA dehydrogenase mRNA in HF and HF+FAT, protein content was unchanged. Though high fat improved myocardial contractile and mitochondrial function in heart failure, these effects of high fat were not evident in sham animals. These studies clearly demonstrate a potential cardioprotective role for high fat during early stages of the progression of heart failure. Future studies should examine the mechanism(s) behind high fat induced alterations in mitochondrial and contractile function in heart failure.


Margaret Chandler, PhD (Advisor)
Nosek Thomas, PhD (Committee Chair)
Hoppel Charles, MD (Committee Member)
Fisher Steven, MD (Committee Member)
Romani Andrea, PhD (Committee Member)
Nagy Laura, PhD (Committee Member)
Kirwan John, PhD (Committee Member)
153 p.

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Rennison, J. (2008). Effects of High Saturated Fat on Myocardial Contractile and Mitochondrial Function in Heart Failure. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Rennison, Julie. "Effects of High Saturated Fat on Myocardial Contractile and Mitochondrial Function in Heart Failure." Electronic Thesis or Dissertation. Case Western Reserve University, 2008. OhioLINK Electronic Theses and Dissertations Center. 02 Sep 2015.

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Rennison, Julie "Effects of High Saturated Fat on Myocardial Contractile and Mitochondrial Function in Heart Failure." Electronic Thesis or Dissertation. Case Western Reserve University, 2008. https://etd.ohiolink.edu/

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