Apolipoprotein A-IV reduced metabolic inflammation in white adipose tissue by inhibiting IKK and JNK signaling in adipocytes
Apolipoprotein A-IV reduced metabolic inflammation in white adipose tissue by inhibiting IKK and JNK signaling in adipocytes
复制标题
载脂蛋白 A-IV 通过抑制脂肪细胞中的 IKK 和 JNK 信号传导来减少白色脂肪组织的代谢炎症
DOI：
10.1016/j.mce.2022.111813
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发表时间：
2022-11-03
影响因子：
4.1
通讯作者：
Li, Xiaoming
中科院分区：
文献类型：
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作者：
Liu, Xiao-Huan;Zhang, Yupeng;Li, Xiaoming
载脂蛋白 A-IV (ApoA-IV) 在饱腹感和血清脂质转运中发挥作用。在饮食诱导肥胖 (DIO) C57BL/6J 小鼠中，ApoA-IV-/-敲除小鼠（KO 小鼠）诱导的 ApoA-IV 缺乏导致体重增加、胰岛素抵抗 (IR) 和血浆游离脂肪酸 (FFA) 增加，而稳定的 ApoA-IVgreen 荧光蛋白 (KO-A4-GFP) 转染可部分逆转这种情况。 老鼠。 DIO KO 小鼠的附睾白色脂肪组织 (eWAT) 以及血液中的 M1 巨噬细胞均增加。基于 RNA 测序分析，与 WT 小鼠相比，DIO ApoA-IV KO 小鼠的 eWAT 中细胞因子-细胞因子受体相互作用、T 细胞和 B 细胞受体，尤其是 IL-17 和 TNF-α 表达上调。在 Raw264.7 巨噬细胞培养测定中，补充 ApoA-IV 可抑制脂多糖 (LPS) 诱导的 IKK 和 JNK 磷酸化。当向 3T3-L1 脂肪细胞补充培养基时，它们表现出对胰岛素的敏感性增加。 ApoAIV 主要通过抑制 M1 巨噬细胞中的 eWAT、IL17-IKK 和 IL17-JNK 活性来预防与肥胖相关的代谢炎症。
Apolipoprotein A-IV (ApoA-IV) plays a role in satiation and serum lipid transport. In diet-induced obesity (DIO) C57BL/6J mice, ApoA-IV deficiency induced in ApoA-IV-/-knock-out (KO mice) resulted in increased bodyweight, insulin resistance (IR) and plasma free fatty acid (FFA), which was partially reversed by stable ApoA-IVgreen fluorescent protein (KO-A4-GFP) transfection in KO mice. DIO KO mice exhibited increased M1 macrophages in epididymal white adipose tissue (eWAT) as well as in the blood. Based on RNA-sequencing analyses, cytokine-cytokine receptor interactions, T cell and B cell receptors, and especially IL-17 and TNF-alpha, were upregulated in eWAT of DIO ApoA-IV KO compared with WT mice. Supplemented ApoA-IV suppressed lipopolysaccharide (LPS)-induced IKK and JNK phosphorylation in Raw264.7 macrophage cell culture assays. When the culture medium was supplemented to 3T3-L1 adipocytes they exhibited an increased sensitivity to insulin. ApoAIV protects against obesity-associated metabolic inflammation mainly through suppression in M1 macrophages of eWAT, IL17-IKK and IL17-JNK activity.