Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats

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Abstract
Summary Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold; 1) to document in rats the effect of streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2) to evaluate the potential effect of a dietary supplementation with fish oil (n-3 fatty acids) on the streptozotocin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the different α- and β-subunits of Na,K-ATPase, and the fatty acid content of total phospholipids. Relative abundance of the mRNAs encoding the α1, α2 and β1 isoforms was studied by Northern blot analysis. Results demonstrated that diabetes significantly decreased activities of α1 and α2 isoforms and mRNA levels of α2 and β1 isoforms, and, at the protein level, increased α1-isoforms and decreased both α2- and β1-isoforms. Changes in fatty acid content of the membrane were consistent with inhibition of desaturase. Fish-oil supplementation produced an increase in membrane incorporation of eicosapentaenoic acid. It also increased the level of β1-isoforms and restored the activity of the α2-isoenzyme without significant changes in the level of α1- and α2-isoforms. Northern blot analysis showed no effect of fish oil supplementation. Experimental diabetes and prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects on the activity and expression of α and β Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequences of diabetes. [Diabetologia (1997) 40: 496–505]

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