Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia

OBJECTIVE - It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesityinduced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients. RESEARCH DESIGN AND METHODS - Peripheral bloodmonocyteswere prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patientswere treated with orwithout EPA treatment (1.8 g daily) for 3months. RESULTS - Monocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, andmonocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator-activated receptor (PPAR)g-dependent pathway. CONCLUSIONS - This study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.