Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin
Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin
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DOI：
10.1210/jc.2004-0436
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发表时间：
2004-10-01
影响因子：
5.8
通讯作者：
Chaudhuri, A
中科院分区：
文献类型：
--
作者：
Dandona, P;Aljada, A;Chaudhuri, A
本研究的目的是确定肥胖患者血浆迁移抑制因子（MIF）浓度和单核细胞（MNC）mRNA是否升高，以及二甲双胍治疗是否降低血浆MIF浓度。40名肥胖受试者[体重指数（BMI），37.5 ± 4.9 kg/m2]和40名非肥胖健康受试者（BMI为22.6 +/- 3.4 kg/m2）的受试者测量其血浆MIF、葡萄糖、胰岛素、游离脂肪酸（FFA）和C反应蛋白（CRP）浓度。16名肥胖患者和16名非肥胖健康受试者具有从MNC制备的RNA。8例血糖浓度正常的肥胖受试者接受二甲双胍1 g（格华止XR; 1000 mg，每日两次）治疗，每日两次，持续6周。8名肥胖受试者作为对照。通过适当的测定法测量葡萄糖、胰岛素、FFA和MIF的血浆浓度。40名肥胖者的空腹MIF浓度为2.8 ± 2.0 ng/ml，而40名非肥胖者的空腹MIF浓度为1.2 ± 0.6 ng/ml（P < 0.001）。血浆MIF浓度与BMI呈显著正相关（r = 0.52; P< 0.001）。MIF mRNA与血浆游离脂肪酸（FFA）和CRP浓度呈显著正相关（r = 0.40; P < 0.05）。8名肥胖受试者在服用二甲双胍缓释制剂前和后1、2、4和6周采集空腹血液样本。6周时平均血药浓度从2.3 ± 1.4 ng/ml降至1.6 ± 1.2 ng/ml（P < 0.05）。未接受二甲双胍治疗的肥胖受试者未显示变化。结论：1）肥胖患者血浆MIF浓度和MNC中MIF mRNA表达升高，与肥胖患者的促炎症状态相一致; 2）MIF的升高与BMI、FFA浓度和CRP有关; 3）二甲双胍可抑制肥胖患者的血浆MIF浓度，提示该药物的抗动脉粥样硬化作用; 4）二甲双胍的这种作用可能有助于潜在的抗动脉粥样硬化作用，这可能与二甲双胍治疗2型糖尿病时观察到的心血管死亡率降低有关。
The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration.Forty obese subjects [ body mass index (BMI), 37.5 +/- 4.9 kg/m(2)] and 40 nonobese healthy subjects ( BMI, 22.6 +/- 3.4 kg/ m(2)) had their plasma MIF, glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP) concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects had RNA prepared from MNCs. Eight obese subjects with normal glucose concentration were treated with metformin 1 g ( Glucophage XR; 1000 mg twice daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma concentration of glucose, insulin, FFAs, and MIF was measured by appropriate assays. mRNA for MIF was measured by real-time PCR.Forty obese subjects had a fasting concentration of MIF of 2.8 +/- 2.0 ng/ml, whereas 40 nonobese subjects had a fasting MIF concentration of 1.2 +/- 0.6 ng/ml ( P < 0.001). Plasma MIF concentrations were significantly related to BMI ( r = 0.52; P< 0.001). mRNA for MIF was correlated to plasma FFAs ( r = 0.40; P < 0.05) and plasma CRP ( r = 0.42; P < 0.05) concentrations. Eight obese subjects had their fasting blood samples taken before and after taking a slow-release preparation of metformin at 1, 2, 4, and 6 wk. The mean plasma concentration fell from 2.3 +/- 1.4 to 1.6 +/- 1.2 ng/ml at 6 wk ( P < 0.05). Obese subjects not on treatment with metformin showed no change. During the period of treatment with metformin, the body weight did not change and the plasma concentration of glucose, insulin, and FFAs did not alter.We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the MNCs are elevated in the obese, consistent with a proinflammatory state in obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive of an antiinflammatory effect of this drug; and 4) this action of metformin may contribute to a potential antiatherogenic effect, which may have implications for the reduced cardiovascular mortality observed with metformin therapy in type 2 diabetes mellitus.