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United States Department of Agriculture

Agricultural Research Service

Title: LOSS OF CARDIAC METABOLIC ADAPTATION AND DYSFUNCTION OF THE HEART WITH WESTERN DIET IN THE OBESE ZUCKER RAT

Author
item Burgmaier, Mathias
item Philip, Femi
item Guthrie, Patrick
item Young, Martin
item Wilson, Christopher
item Taegtmeyer, Heinrich

Submitted to: Diabetes
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2006
Publication Date: 6/1/2006
Citation: Burgmaier, M., Philip, F., Guthrie, P., Young, M.E., Wilson, C.R., Taegtmeyer, H. 2006. Loss of cardiac metabolic adaptation and dysfunction of the heart with western diet in the obese Zucker rat [abstract]. Diabetes. 55(Suppl.1):A388.

Interpretive Summary:

Technical Abstract: The normal heart sustains its work output through changing the proportion of substrates it oxidizes depending on fuel supply. This metabolic adaptation is thought to be regulated at a transcriptional level by the peroxisome proliferator-activated receptor alpha (PPAR-alpha). We proposed that obesity may alter PPAR-alpha regulated gene expression, may lead to a loss of metabolic adaptation, and may cause contractile dysfunction of the heart. Male obese and lean Zucker rats (eight weeks old) were fed either Western (45 kcal% fat) or Control (10 kcal% fat) diet for seven days. Hearts were isolated and perfused as working hearts with physiologic concentrations of glucose, oleate, and insulin. Non-perfused hearts were used for transcript analysis by real-time quantitative RT-PCR and histology. Contractile function decreased in hearts of obese rats fed Western diet. In the obese rats fed Western diet, there was a smaller increase in oleate oxidation when compared to lean controls. There were no changes in mRNA transcript levels of the PPAR-alpha regulated genes investigated (pyruvate dehydrogenase kinase-4, uncoupling protein-3, mitochondrial and cytosolic thioesterases) when Zucker obese rats were fed Western diet. Hearts from lean rats fed a Western diet showed increased transcript levels of PPAR-alpha regulated genes, oleate oxidation and maintained cardiac function. In conclusion, hearts from obese Zucker rats fed Western diet are unable to increase PPAR-alpha regulated gene transcripts and rates of oleate oxidation. This loss of metabolic adaptation is associated with contractile dysfunction. The findings suggest a link between diet and cardiac energetics and provide a possible mechanism for cardiac dysfunction in an animal model of genetic obesity.

Last Modified: 06/26/2017
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