Effect of eicosapentaenoic acid on glucose-induced diacylglycerol synthesis in cultured bovine aortic endothelial cells

Hyperglycemia has been postulated to increase diacylglycerol (DAG) level through de novo synthesis pathway and subsequently activate protein kinase C (PKC) in vascular cells, possibly leading to vascular dysfunction associated with diabetes, In this study, we examined the effect of eicosapentaenoic acid (EPA) on high glucose-induced increase in DAG level in cultured aortic endothelial cells (ECs), In ECs, total DAC; level was significantly increased in the cells cultured with high glucose levels (400 mg/dl) compared with the cells with normal glucose levels (100 mg/dl), The addition of EPA completely prevented high glucose-induced increase in total DAG level. In contrast, other common fatty acids such as palmitate and oleate significantly stimulated DAG; syntheisis, although arachidonate did not affect it. High glucose level significantly stimulated the incorporation of H-3-palmitate into DAG, while it did not affect the incorporation of H-3-arachidonate into DAG;, The addition of EPA completely prevented the high glucose-induced increase in 3H-palmitate incorporation into DAG, while it did not affect the H-3-arachidonate incorporation, These findings suggest that EPA can prevent high glucose induced-increase in DAG: level in ECs, probably by specifically inhibiting de novo synthesis at the step of acylation, EPA may be one of the candidates for clinical agents normalizing activation of DAG-PKC pathway in diabetic vascular tissues and preventing vascular complications associated with diabetes. (C) 1998 Academic Press.