Yuan J, Wang Y, Gao J, Zhang X, Xing J
Department of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital, Lubei District, Tangshan, Hebei, People's Republic of China.
Physiol Res. 2024 Mar 11;73(1):57-68. doi: 10.33549/physiolres.935113.
This study investigated the effect of eicosapentaenoic acid (EPA) on insulin resistance in pregnant mice with gestational diabetes mellitus (GDM) and underlying mechanism. C57BL/6 mice fed with a high-fat diet for 4 weeks and the newly gestated were selected and injected with streptozotocin for GDM modeling. We demonstrated that the fasting insulin levels (FINS) and insulin sensitivity index (ISI) in serum and blood glucose level were significantly higher in GDM group than in normal control (NC) group. The low or high dose of EPA intervention reduced these levels, and the effect of high dose intervention was more significant. The area under the curve in GDM group was higher than that of NC group, and then gradually decreased after low or high dose of EPA treatment. The serum levels of TC, TG and LDL were increased in GDM group, while decreased in EPA group. GDM induced down-regulation of HDL level, and the low or high dose of EPA gradually increased this level. The levels of p-AKT2Ser, p-IRS-1Tyr, GLUT4, and ratios of pIRS-1Tyr/IRS-1 and pAKT2Ser/AKT2 in gastrocnemius muscle were reduced in GDM group, while low or high dose of EPA progressively increased these alterations. GDM enhanced TLR4, NF-kappaB p65, IL-1beta, IL-6 and TNF-alpha levels in placental tissues, and these expressions were declined at different dose of EPA, and the decrease was greater at high dose. We concluded that EPA receded the release of inflammatory factors in the placental tissues by inhibiting the activation of TLR4 signaling, thereby alleviating the IR.
本研究探讨了二十碳五烯酸(EPA)对妊娠期糖尿病(GDM)孕鼠胰岛素抵抗的影响及其潜在机制。选取喂食高脂饮食4周的C57BL/6小鼠及新受孕小鼠,注射链脲佐菌素进行GDM建模。我们发现,GDM组血清中的空腹胰岛素水平(FINS)、胰岛素敏感性指数(ISI)和血糖水平显著高于正常对照组(NC)。低剂量或高剂量的EPA干预降低了这些水平,且高剂量干预的效果更显著。GDM组的曲线下面积高于NC组,在低剂量或高剂量EPA治疗后逐渐降低。GDM组血清TC、TG和LDL水平升高,而EPA组降低。GDM导致HDL水平下调,低剂量或高剂量的EPA使其水平逐渐升高。GDM组腓肠肌中p-AKT2Ser、p-IRS-1Tyr、GLUT4水平以及pIRS-1Tyr/IRS-1和pAKT2Ser/AKT2的比值降低,而低剂量或高剂量的EPA使这些改变逐渐增加。GDM增强了胎盘组织中TLR4、NF-κB p65、IL-1β、IL-6和TNF-α的水平,不同剂量的EPA使这些表达下降,高剂量时下降幅度更大。我们得出结论,EPA通过抑制TLR4信号通路的激活,减少了胎盘组织中炎症因子的释放,从而减轻了胰岛素抵抗。