National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital, Xi'an Jiaotong University, Western China Science & Technology Innovation Harbour, Xi'an, China.
National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital, Xi'an Jiaotong University, Western China Science & Technology Innovation Harbour, Xi'an, China; Department of Gastrointestinal Surgery, the Affiliated Taian City Central Hospital, Qingdao University, Taian, China.
Mol Cell Endocrinol. 2023 Jan 1;559:111813. doi: 10.1016/j.mce.2022.111813. Epub 2022 Oct 29.
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-IV-green 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-α, were up-regulated 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. ApoA-IV protects against obesity-associated metabolic inflammation mainly through suppression in M1 macrophages of eWAT, IL17-IKK and IL17-JNK activity.
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 缺陷导致 ApoA-IV-/-敲除（KO）小鼠体重增加、胰岛素抵抗（IR）和血浆游离脂肪酸（FFA）增加，而稳定的 ApoA-IV-绿色荧光蛋白（KO-A4-GFP）转染在 KO 小鼠中部分逆转了这一现象。DIO KO 小鼠的附睾白色脂肪组织（eWAT）和血液中的 M1 巨噬细胞增加。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，特别是白细胞介素 17（IL-17）和肿瘤坏死因子-α（TNF-α）上调。补充 ApoA-IV 可抑制 Raw264.7 巨噬细胞培养物中脂多糖（LPS）诱导的 IKK 和 JNK 磷酸化。当培养基补充到 3T3-L1 脂肪细胞中时，它们对胰岛素的敏感性增加。ApoA-IV 通过抑制 eWAT 中的 M1 巨噬细胞、IL17-IKK 和 IL17-JNK 活性来预防肥胖相关的代谢性炎症。
