Abstract 1589: “Western” Diet, but not High Fat Diet, Causes Maladaptation of Cardiac Fatty Acid Metabolism and Cardiac Dysfunction in the Wistar Rat
Obesity and diabetes are associated with increased fatty acid availability in excess of fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction. We tested the hypothesis that a “western” or a high fat diet will lead to maladaptation of cardiac fatty acid oxidation and subsequent contractile dysfunction. Male Wistar rats (n=12–17/group) were fed a control, western, or high fat diet (10%, 45%, or 60% calories from fat, respectively) for acute (1 day and 1 week), short (1–2 months), intermediate (4 – 6 months), or long (8–12 months) term. In one set of rats, cardiac power, glucose oxidation and oleate oxidation were assessed in isolated working hearts. In parallel experiments, hearts were isolated for quantitative RT-PCR mRNA transcript analysis. Cardiac power decreased with the western diet (−24%, p<0.05). There was no significant decrease in cardiac power with the high fat diet. Oleate oxidation was increased with western diet in the acute (+17%), short (+36%) and intermediate term (+31%) (p<0.01), but not in the long term. In contrast, oleate oxidation was increased with the high fat diet at all time points investigated (+38%, +44%, +62%, and +15% for acute, short, intermediate, and long term, respectively; p<0.05). There was a sustained decrease in glucose oxidation with western diet by 38% (p<0.05) which was coincident with a sustained induction of the mRNA encoding for pyruvate dehydrogenase kinase 4 (PDK4) by 68% (p<0.01). Glucose oxidation was similarly decreased with high fat diet by 42% (p<0.05), which was coincident with a sustained induction of the mRNA encoding for PDK4 by 266% (p<0.01). mRNA transcripts for genes involved in fatty acid-mediated futile cycling, such as cytosolic thioesterase 1 (CTE-1), were upregulated to a greater extent by the high fat diet (CTE-1 average +551%, p<0.001), as compared to the western diet (CTE-1 average +296%, p<0.001). In conclusion, a greater activation of oleate oxidation and PPARγ-regulated gene expression in the hearts of rats fed a high fat diet, as compared to a western diet, is coincident with maintenance of cardiac function. This implicates inadequate activation of PPARα with the western diet in the development of cardiac dysfunction.