INTERLEUKIN-6 DEFICIENCY MODIFIES THE EFFECT OF HIGH FAT DIET ON MYOCARDIAL EXPRESSION OF FATTY ACID TRANSPORTERS AND MYOCARDIAL LIPIDS

摘要

Chronic inflammation is a critical feature of obesity in the development of myocardial dysfunction. The observations that interleukin-6 (IL-6) is implicated in lipid and glucose homeostasis as well as its connection with the pathogenesis of insulin resistance might suggest the involvement of this cytokine in metabolic disorders of the failing heart. In the present study we aimed to assess the effects of IL-6 ablation in mice fed with normal and high fat diet on the myocardial expression of glucose and fatty acid transporting proteins, and to evaluate the paralleled alterations in lipid content. We demonstrated that mice devoid of IL-6 exert reduced glucose transporter type 4 (GLUT-4) expression (–26%) and plasma membrane abundance (–43%), with no effect on glucose transporter type 1 (GLUT-1) content. Although there were no significant alterations in fatty acid translocase (FAT/CD36) and plasma membrane-associated fatty acid-binding protein (FABPpm) levels, we revealed a substantial decline in intramyocardial triacylglycerol level (–49%). Challenging of IL-6 knockout (KO) mice with high fat diet evoked an increase in FAT/CD36 expression (+19%) concomitantly with a trend for its reduced amount in plasma and mitochondrial membranes. Additionally, an increase in triacylglycerol level (+56%) was noticed, simultaneously with elevated content of saturated (+62%), monounsaturated (+69%) and polyunsaturated (+38%) fatty acids in this lipid fraction. The presented data reflect different roles of IL-6 in cardiomyocytes under selected conditions (i.e., normal and excessive lipid supply).