Submitted to: Biochemical Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2007
Publication Date: 9/15/2007
Citation: Wilson, C.R., Tran, M.K., Salazar, K.L., Young, M.E., Taegtmeyer, H. 2007. Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats. Biochemical Journal. 406(3):457-467. Interpretive Summary: Conditions associated with prolonged elevations in blood fat levels have been associated with heart disease development in humans. However, the time course of heart disease development following prolonged high-fat feeding is lacking in rodent models. This is a fundamental question if rodent models are to be used for investigating the heart disease observed in humans. The present study shows that feeding a rat a calorie-rich diet, composed of both glucose and fat (called a Western diet) leads to heart disease in approximately 1 year. In contrast, feeding a rat a calorie-rich diet, composed of primarily fat (similar to the Atkin's diet) does not lead to heart disease within the 1-year period studied. These results show that both glucose and fat are required to cause heart disease.
Technical Abstract: Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal muscle insulin resistance. We tested the hypothesis that "western" and high-fat diets differentially cause maladaptation of cardiac and skeletal muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed low-fat, "western," or high-fat (10%, 45%, or 60% calories from fat, respectively) diet for acute (1 day to 1 week), short (4 to 8 weeks), intermediate (16 to 24 weeks), or long (32 to 48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high-fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with western diet in the acute, short, and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either western or high-fat feeding. Fatty acid-responsive genes, including pyruvate dehydrogenase kinase 4 and cytosolic thioesterase 1, increased in heart and soleus muscle to a greater extent with feeding a high-fat diet, versus a western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with western diet.