Long-term regulation of pyruvate dehydrogenase kinase by high-fat feeding. Experiments in vivo and in cultured cardiomyocytes.

The provision of the high-fat diet (47% of calories as fat) for 28 days evoked a significant decline in cardiac PDHa activity, together with marked increases in the activity of PDH kinase measured in isolated mitochondria and freshly-prepared cardiomyocytes from adult rats. Plasma insulin concentrations in fat-fed rats were not significantly different from control, but plasma NEFA concentrations were elevated. PDH kinase activity in cardiomyocytes from fat-fed rats fell substantially in culture (25 h). This decline was prevented by the inclusion of n-octanoate and DBcAMP in combination, but not individually, in the culture medium. The results are discussed in relation to the role for fatty acids and insulin in the long-term modulation of cardiac PDH kinase activity by high-fat feeding.