Anti-inflammatory effects of anti-insulin resistant drugs and monocyte functional analysis in visceral obesity

在本研究中，为了阐明脂肪细胞-巨噬细胞相互作用的分子机制，我们研究了肥胖和代谢综合征中脂肪细胞因子失调与单核细胞功能的关系以及抗胰岛素抵抗药物对单核细胞功能的影响。结果1.用THP-1细胞检测：在THP-1细胞中，PPAR配体TZDS(吡格列酮6μM)作用24小时可显著降低IL-6和MMP9的表达，EPA50μM作用24小时可显著降低THP-1细胞中CD14、肿瘤坏死因子α、单核细胞趋化蛋白1、MMP9和TLR4的表达，升高脂联素水平。人单核细胞检测：对照组、肥胖组和糖尿病组外周血单核细胞经MACS或Ficoll-Paque法分离后进行单核细胞功能检测。(1)实时定量聚合酶链式反应检测肥胖组和糖尿病组单核细胞中肿瘤坏死因子-α、IL-6和单核细胞趋化蛋白-1的表达均高于正常对照组。(2)单核细胞特异性标志物CD14的表达和活性在肥胖组和对照组之间无显著差异，而糖尿病组CD14和失活的M2巨噬细胞的表达和活性显著低于肥胖组。(3)TZDS治疗3个月后，肿瘤坏死因子-α的表达和CD14活性均有不同程度的提高。临床研究：我们发现，在肥胖啮齿动物模型和人类肥胖受试者中，高纯度的EPA可以减少小而密的低密度脂蛋白(SdLDL)、残留物和CRP(糖尿病护理27：144,2007)，并增加脂联素的分泌，可能是通过改善肥胖相关的脂肪组织炎症(ATVB 27：1918,2007)。

In the present study, to elucidate the molecular mechanisms of adipocyte-macrohphage interaction, we examined the relationship between adipocytokine dysregulation and the function of monocyte and the effect of anti-insulin resistant agents on the function of monocyte in the obesity and metabolic syndrome.1. Examination using the THP-1 cell : In THP-1 cell, the incubation with of PPAR ligand ; TZDs(Pioglitazone 6μM) for 24 hours significantly decreased the expression of IL-6 and MMP-9 and the administration of EPA 50 μM for 24 hours significantly decreased CD14, TNFα, MCP-1, MMP-9 and TLR4 and increased adiponectin.2. Examination using the human monocyte : We examined monocyte function after separating peripheral blood monocyte cells by MACS or Ficoll-Paque method from blood in control, obesity and diabetes. (1) The expressions of TNF-α, IL-6 and MCP-1 detected by real-time PCR in monocyte were higher in obesity and diabetes compared to control. (2) there is no significant difference between the expression and activity of CD14, a specific marker of monocyte, detected by FACS between control and obesity, however in diabetic patients the expression and activity of CD14 and inactive M2 Macrophage was significantly lower. (3) Administrating TZDs for 3 months, the expression of TNF-α and CD14 activity were improved3. Clinical Study : We revealed that highly purified EPA reduces small, dense LDL(sdLDL), remnants, and CRP(Diabetes Care 27 : 144, 2007) and increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of obese-related adipose tissue inflammation(ATVB 27 : 1918, 2007).