Department of Obstetrics, Zibo Central Hospital, No.54 of Gongqingtuan West Road, Zhangdian District, Zibo 255000, Shandong, China.
Department of Obstetrics, Zibo Central Hospital, No.54 of Gongqingtuan West Road, Zhangdian District, Zibo 255000, Shandong, China.
Prostaglandins Leukot Essent Fatty Acids. 2020 Dec;163:102213. doi: 10.1016/j.plefa.2020.102213. Epub 2020 Nov 18.
Fatty acid binding protein 4 (FABP4) was found to be closely correlated with gestational diabetes mellitus (GDM), a severe pregnancy syndrome. However, safe and efficient treatment for GDM is limited. We aimed to investigate whether inhibition of FABP4 could ameliorate GDM and the underlying mechanism. An evaluation of blood samples from a total of 109 patients showed significantly positive correlations between serum FABP4 and biochemical parameters known to associate with GDM. This correlation was subsequently explored in vitro. FABP4 inhibition was achieved using BMS309403 in GDM mice. GDM related symptoms, including insulin resistance and macrophage infiltration in the adipose tissues, were measured. Lipid metabolism in 3T3-L1 adipocytes was tested. We firstly confirmed the positive correlations between serum FABP4, insulin resistance and inflammation cytokines, including tumor necrosis factor-α (TNF) and interleukin-6 (IL-6), in GDM patients. Surprisingly, inhibition of FABP4 by BMS309403 resulted in significant alleviation of GDM symptoms in GDM mouse model. BMS309403 improved glucose and insulin tolerance and transcriptionally repressed the levels of TNF-α and IL-6, suggesting a role of FABP4 in inflammation. Furthermore, macrophage infiltration into the adipose tissues was dramatically decreased in the BMS309403-treated GDM mice compared to untreated GDM mice. Interestingly, incubation of 3T3-L1 adipocytes with FABP4 protein decreased the mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ), which was absent when BMS309403 was used. However, lipid accumulation was promoted in FABP4-treated 3T3-L1 adipocytes which showed no change in the presence of BMS309403. In conclusion, inhibition of FABP4 by BMS309403 could be an effective treatment to alleviate GDM.
脂肪酸结合蛋白 4（FABP4）与妊娠糖尿病（GDM）密切相关，GDM 是一种严重的妊娠综合征。然而，针对 GDM 的安全且有效的治疗方法有限。我们旨在研究抑制 FABP4 是否可以改善 GDM 及其潜在机制。对总共 109 名患者的血液样本进行评估，结果显示血清 FABP4 与已知与 GDM 相关的生化参数之间存在显著正相关。随后在体外对其进行了研究。在 GDM 小鼠中使用 BMS309403 抑制 FABP4。测量 GDM 相关症状，包括胰岛素抵抗和脂肪组织中巨噬细胞浸润。测试了 3T3-L1 脂肪细胞中的脂质代谢。我们首先证实了血清 FABP4、胰岛素抵抗和炎症细胞因子（包括肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6））之间在 GDM 患者中的正相关关系。令人惊讶的是，BMS309403 抑制 FABP4 可显著改善 GDM 小鼠模型中的 GDM 症状。BMS309403 改善了葡萄糖和胰岛素耐量，并转录抑制了 TNF-α和 IL-6 的水平，表明 FABP4 具有炎症作用。此外，与未治疗的 GDM 小鼠相比，BMS309403 处理的 GDM 小鼠的脂肪组织中巨噬细胞浸润显著减少。有趣的是，用 FABP4 蛋白孵育 3T3-L1 脂肪细胞会降低过氧化物酶体增殖物激活受体 γ（PPARγ）的 mRNA 和蛋白水平，而当使用 BMS309403 时则不会。然而，在 FABP4 处理的 3T3-L1 脂肪细胞中促进了脂质积累，而在存在 BMS309403 的情况下则没有变化。总之，BMS309403 抑制 FABP4 可能是缓解 GDM 的有效治疗方法。
