Younsi Mohamed, Quilliot Didier, Al-Makdissy Nehmann, Delbachian Irène, Drouin Pierre, Donner Mireille, Ziegler Olivier
Laboratory of Nutrition and Metabolic Diseases, Medical School, Université Henri-Poincaré (UHP), Vandoeuvre les Nancy, France.
Metabolism. 2002 Oct;51(10):1261-8. doi: 10.1053/meta.2002.35184.
The complex mechanisms by which obesity predisposes to insulin resistance are not clearly understood. According to a cell membrane hypothesis of insulin resistance, the defects in insulin action could be related to changes in membrane properties. The purpose of this work was to examine the relationship between 2 markers of insulin resistance (fasting plasma insulin [FPI] and homeostasis model assessment [HOMA IR]) and erythrocyte membrane lipid composition. In the first cross-sectional study, 24 premenopausal nondiabetic overweight women (body mass index [BMI], 32.5 +/- 0.9 kg/m(2); age, 35.7 +/- 2.2 years) were compared to 21 lean healthy women (BMI, 21 +/- 0.4 kg/m(2); age, 35.4 +/- 2.2 years). The second study examined whether a 3-month diet-induced weight loss, which usually improves insulin resistance, could also affect the membrane phospholipid (PL) composition and fluidity in the overweight group. Overweight women had significantly higher FPI levels (P <.0001), HOMA IR (P <.0001), membrane sphingomyelin (SM) (P <.05), and cholesterol (P <.05) contents than lean women. Baseline FPI and HOMA IR were positively correlated with membrane SM (P <.005), phosphatidylethanolamine (PE) (P <.005), and phosphatidylcholine (PC) (P <.05) contents, and negatively with phosphatidylinositol (PI) (P <.05) contents in the whole population. Multivariate regression analyses showed that 2 membrane parameters, PE and SM, were among the independent predictors of FPI or HOMA IR in the whole population, but also in the lean and the obese groups separately. Intervention induced a significant reduction in body weight (-5.7% +/- 0.7%), fat mass (-11.3% +/- 1.4%), and FPI (-10.2% +/- 5.4%). An improvement in membrane lipid composition was only observed in the insulin resistant subgroup (FPI > 9.55 mU/L). The reduction in FPI or HOMA IR was directly associated with reduction in SM and PE contents, a finding independent of the reduction in fat mass. A stepwise multiple regression analysis indicated that the changes in SM accounted for 26.6% of the variance in the changes in FPI as an independent predictor, with the changes in fat mass and PE as other determinants (27.8% and 20%, respectively, adjusted r(2) =.704, P <.0001). These results suggest that the abnormalities in the membrane PL composition could be included in the unfavorable lipid constellation of obesity which correlated with impaired insulin sensitivity.
肥胖易引发胰岛素抵抗的复杂机制尚不清楚。根据胰岛素抵抗的细胞膜假说,胰岛素作用的缺陷可能与膜特性的变化有关。本研究的目的是探讨胰岛素抵抗的两个标志物(空腹血浆胰岛素[FPI]和稳态模型评估[HOMA-IR])与红细胞膜脂质组成之间的关系。在第一项横断面研究中,将24名绝经前非糖尿病超重女性(体重指数[BMI],32.5±0.9kg/m²;年龄,35.7±2.2岁)与21名瘦的健康女性(BMI,21±0.4kg/m²;年龄,35.4±2.2岁)进行比较。第二项研究考察了通常能改善胰岛素抵抗的3个月饮食诱导体重减轻是否也会影响超重组的膜磷脂(PL)组成和流动性。超重女性的FPI水平(P<.0001)、HOMA-IR(P<.0001)、膜鞘磷脂(SM)(P<.05)和胆固醇(P<.05)含量显著高于瘦女性。在整个人群中,基线FPI和HOMA-IR与膜SM(P<.005)、磷脂酰乙醇胺(PE)(P<.005)和磷脂酰胆碱(PC)(P<.05)含量呈正相关,与磷脂酰肌醇(PI)(P<.05)含量呈负相关。多变量回归分析表明,膜参数PE和SM是整个人群中FPI或HOMA-IR的独立预测因子,在瘦组和肥胖组中也是如此。干预导致体重显著降低(-5.7%±0.7%)、脂肪量(-11.3%±1.4%)和FPI(-10.2%±5.4%)降低。仅在胰岛素抵抗亚组(FPI>9.55mU/L)中观察到膜脂质组成的改善。FPI或HOMA-IR的降低与SM和PE含量的降低直接相关,这一发现与脂肪量的降低无关。逐步多元回归分析表明,作为独立预测因子,SM的变化占FPI变化方差的26.6%,脂肪量和PE的变化为其他决定因素(分别为27.8%和20%,调整后r²=.704,P<.0001)。这些结果表明,膜PL组成的异常可能包含在与胰岛素敏感性受损相关的肥胖不良脂质组合中。