Division of Diabetic Research, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.
Diabetes Care. 2012 Dec;35(12):2631-9. doi: 10.2337/dc12-0269. Epub 2012 Aug 21.
It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced 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.
Peripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months.
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, and monocyte 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)γ-dependent pathway.
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.
最近有研究表明,肥胖症中促炎(M1)巨噬细胞多于抗炎(M2)巨噬细胞,从而导致肥胖引起的脂肪炎症和胰岛素抵抗。最近的一项临床试验表明,高度纯化的二十碳五烯酸(EPA)可降低主要冠状动脉事件的发生率。在这项研究中,我们研究了 EPA 对肥胖血脂异常患者外周血单核细胞 M1/M2 样表型的影响。
从 26 名肥胖无血脂异常患者和 90 名肥胖血脂异常患者中分离外周血单核细胞。在这 90 名肥胖血脂异常患者中,82 名患者接受或不接受 EPA 治疗(每天 1.8 克)3 个月。
与无血脂异常的患者相比,血脂异常的肥胖患者的单核细胞中白细胞介素-10(IL-10)的表达明显降低,IL-10 是 M2 标志物。与对照组相比,EPA 可显著增加血清 IL-10 和 EPA 水平、EPA/花生四烯酸(AA)比值以及单核细胞 IL-10 表达,降低脉搏波速度(PWV),PWV 是动脉僵硬的指标。EPA 治疗后,血清 EPA/AA 比值与单核细胞 IL-10 表达呈显著正相关。只有单核细胞 IL-10 表达和血清脂联素的增加是 EPA 降低 PWV 的独立决定因素。此外,EPA 通过过氧化物酶体增殖物激活受体(PPAR)γ 依赖性途径显著增加人单核细胞 THP-1 细胞中 IL-10 的表达和分泌。
本研究首次表明,EPA 增加单核细胞 IL-10 表达与降低动脉僵硬平行,这可能有助于 EPA 在肥胖血脂异常患者中的抗动脉粥样硬化作用。