Chattopadhyay Arnab, Navab Mohamad, Hough Greg, Grijalva Victor, Mukherjee Pallavi, Fogelman Hannah R, Hwang Lin H, Faull Kym F, Lusis Aldons J, Reddy Srinivasa T, Fogelman Alan M
Departments of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736.
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736.
J Lipid Res. 2016 May;57(5):832-47. doi: 10.1194/jlr.M064352. Epub 2016 Mar 9.
Mouse chow supplemented with lysophosphatidylcholine with oleic acid at sn-1 and a hydroxyl group at sn-2 (LysoPC 18:1) increased LysoPC 18:1 in tissue of the jejunum of LDL receptor (LDLR)-null mice by 8.9 ± 1.7-fold compared with chow alone. Western diet (WD) contained dramatically less phosphatidylcholine 18:1 or LysoPC 18:1 compared with chow, but feeding WD increased LysoPC 18:1 in the jejunum by 7.5 ± 1.4-fold compared with chow. Feeding LysoPC 18:1 or feeding WD increased oxidized phospholipids in the jejunum by 5.2 ± 3.0-fold or 8.6 ± 2.2-fold, respectively, in LDLR-null mice (P < 0.0004), and 2.6 ± 1.5-fold or 2.4 ± 0.92-fold, respectively, in WT C57BL/6J mice (P < 0.0001). Adding 0.06% by weight of a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) decreased LysoPC 18:1 in the jejunum of LDLR-null mice on both diets (P < 0.0001), and prevented the increase in oxidized phospholipids in the jejunum in LDLR-null and WT mice on both diets (P < 0.008). Tg6F decreased inflammatory cells in the villi of the jejunum, decreased dyslipidemia, and decreased systemic inflammation in LDLR-null and WT mice on both diets. We conclude that Tg6F reduces diet-induced inflammation by reducing the content of unsaturated LysoPC and oxidized phospholipids in the jejunum of mice.
在LDL受体(LDLR)基因敲除小鼠的空肠组织中,补充了在sn-1位带有油酸且在sn-2位带有羟基的溶血磷脂酰胆碱(LysoPC 18:1)的小鼠饲料,与单独的普通饲料相比,使LysoPC 18:1增加了8.9±1.7倍。与普通饲料相比,西方饮食(WD)中的磷脂酰胆碱18:1或LysoPC 18:1含量显著更低,但与普通饲料相比,喂食WD使空肠中的LysoPC 18:1增加了7.5±1.4倍。在LDLR基因敲除小鼠中,喂食LysoPC 18:1或喂食WD分别使空肠中的氧化磷脂增加了5.2±3.0倍或8.6±2.2倍(P<0.0004),在野生型C57BL/6J小鼠中分别增加了2.6±1.5倍或2.4±0.92倍(P<0.0001)。添加0.06%重量的表达6F肽的转基因番茄浓缩物(Tg6F)可降低两种饮食喂养的LDLR基因敲除小鼠空肠中的LysoPC 18:1(P<0.0001),并防止两种饮食喂养的LDLR基因敲除小鼠和野生型小鼠空肠中氧化磷脂的增加(P<0.008)。Tg6F可减少两种饮食喂养的LDLR基因敲除小鼠和野生型小鼠空肠绒毛中的炎症细胞,降低血脂异常,并减轻全身炎症。我们得出结论,Tg6F通过降低小鼠空肠中不饱和LysoPC和氧化磷脂的含量来减轻饮食诱导的炎症。