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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

item Burgmaier, Mathias - UNIV OF GOTTINGEN-GERMANY
item Guthrie, Patrick - BAYLOR COLLEGE OF MED
item Young, Martin
item Wilson, Christopher - UT-HOUSTON HLTH SCI CENTR
item Taegtmeyer, Heinrich - UT-HOUSTON HLTH SCI CENTR

Submitted to: Diabetes
Publication Type: Abstract Only
Publication Acceptance Date: February 1, 2006
Publication Date: June 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.

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: 4/22/2015
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