Departments of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
Molecular Toxicology Interdepartmental Program, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095.
J Lipid Res. 2018 Oct;59(10):1818-1840. doi: 10.1194/jlr.M083527. Epub 2018 Aug 23.
After crossing floxed stearoyl-CoA desaturase-1 () mice with LDL receptor-null () mice, and then Villin Cre () mice, enterocyte expression in // mice was reduced 70%. On Western diet (WD), / mice gained more weight than // mice ( < 0.0023). On WD, jejunum levels of lysophosphatidylcholine (LysoPC) 18:1 and lysophosphatidic acid (LPA) 18:1 were significantly less in // compared with / mice ( < 0.0004 and < 0.026, respectively). On WD, // mice compared with / mice had lower protein levels of lipopolysaccharide-binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4), and myeloid differentiation factor-88 (MyD88) in enterocytes and plasma, and less dyslipidemia and systemic inflammation. Adding a concentrate of tomatoes transgenic for the apoA-I mimetic peptide 6F (Tg6F) to WD resulted in reduced enterocyte protein levels of LBP, CD14, TLR4, and MyD88 in / mice similar to that seen in // mice. Adding LysoPC 18:1 to WD did not reverse the effects of enterocyte knockdown. Adding LysoPC 18:1 (but not LysoPC 18:0) to chow induced jejunum expression and increased dyslipidemia and plasma serum amyloid A and interleukin 6 levels in / mice, but not in // mice. We conclude that enterocyte is partially responsible for LysoPC 18:1- and WD-induced dyslipidemia and inflammation in mice.
在将 floxed 硬脂酰辅酶 A 去饱和酶-1 () 小鼠与 LDL 受体缺失 () 小鼠杂交,然后再与 Villin Cre () 小鼠杂交后,回肠细胞中的表达减少了 70%。在西方饮食 (WD) 中,/ 小鼠比 // 小鼠体重增加更多(<0.0023)。在 WD 条件下,// 小鼠空肠中溶血磷脂酰胆碱 (LysoPC) 18:1 和溶血磷脂酸 (LPA) 18:1 的水平明显低于 / 小鼠(<0.0004 和 <0.026,分别)。在 WD 条件下,与 / 小鼠相比,// 小鼠空肠和血浆中的脂多糖结合蛋白 (LBP)、分化簇 14 (CD14)、Toll 样受体 4 (TLR4) 和髓样分化因子-88 (MyD88) 的蛋白水平较低,且脂代谢紊乱和全身炎症较轻。在 WD 中添加富含 apoA-I 模拟肽 6F 的转基因番茄浓缩物(Tg6F),可使 / 小鼠的空肠 LBP、CD14、TLR4 和 MyD88 蛋白水平降低,与 // 小鼠相似。在 WD 中添加 LysoPC 18:1 并不能逆转敲低回肠细胞的作用。在 WD 中添加 LysoPC 18:1(而非 LysoPC 18:0)可诱导 / 小鼠空肠表达,并增加脂代谢紊乱和血浆血清淀粉样蛋白 A 和白细胞介素 6 水平,但在 // 小鼠中则没有。我们的结论是,回肠细胞中的是部分负责 LysoPC 18:1 和 WD 诱导的脂代谢紊乱和炎症反应的发生。