Abstract 1125: Differential Influence of Distinct Fatty Acids on Cardiomyocyte Metabolic Gene Expression
Diabetes mellitus increases risk for cardiovascular disease, and exposes the heart to high plasma fatty acid (FA) levels, which induce genes promoting FA oxidation (e.g. malonyl-CoA decarboxylase; mcd), as well as those suppressing carbohydrate oxidation (e.g. pyruvate dehydrogenase kinase 4; pdk4). Little is known regarding the time course and magnitude of the effects of distinct FA species on the expression of metabolic genes in the cardiomyocytes of the heart. As such, the time- (3, 6, 12, 24, and 48 hrs) and concentration- (0.1, 0.2, and 0.4 mM) dependent effects of octanoate (8:0), palmitate (16:0), stearate (18:0), oleate (18:1), and linoleic acid (18:2) on metabolic gene expression were investigated in isolated adult rat cardiomyocytes (ARCs). Five known FA-responsive genes were studied; cytosolic thioesterase 1 (cte1), mitochondrial thioesterase 1 (mte1), mcd, pdk4, and uncoupling protein 3 (ucp3). The general order of responsiveness of ARCs to the FAs investigated, in terms of initial rates of induction of FA-responsive genes, was oleate>stearate>palmitate≥linoleic>octanoate (see Figure⇓ for effects of 0.4mM FAs on pdk4). The effects of stearate and palmitate tended to be transient (i.e. initial high induction, followed by subsequent repression), while oleate and linoleic acid caused relatively sustained induction of metabolic genes (see Figure⇓). Gene specific effects were also observed; palmitate exhibited relatively small effects on ucp3, as compared to the other genes investigated. These findings may explain why diets high in unsaturated FAs (e.g. oleate) are cardioprotective, while diets rich in saturated FAs (e.g. palmitate) are not.