Journal
BIOCHEMICAL JOURNAL
Volume 406, Issue -, Pages 457-467Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20070392
Keywords
cardiac function; cardiac metabolism; diet-induced obesity; futile cycling; gene expression; triacylglycerol
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Funding
- NHLBI NIH HHS [R01-HL073162, HL074259, R01 HL061483, R01 HL074259, R01 HL073162] Funding Source: Medline
- NIDDK NIH HHS [T35 DK007676] Funding Source: Medline
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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 on low fat, `Western' or high fat (10, 45 or 60 % calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 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 PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with 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.
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