Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum

被引：11

作者：

Mukherjee, Pallavi ^{[1
,2
]}

Hough, Greg ^{[1
,2
]}

Chattopadhyay, Arnab ^{[1
,2
]}

Navab, Mohamad ^{[1
,2
]}

Fogelman, Hannah R. ^{[1
,2
]}

Meriwether, David ^{[3
]}

Williams, Kevin ^{[3
]}

Bensinger, Steven ^{[3
]}

Moller, Travis ^{[8
]}

Faull, Kym F. ^{[8
]}

Lusis, Aldons J. ^{[1
,2
,4
,5
]}

Iruela-Arispe, M. Luisa ^{[9
]}

Bostrom, Kristina I. ^{[1
,2
]}

Tontonoz, Peter ^{[6
,10
]}

Reddy, Srinivasa T. ^{[1
,2
,3
,7
]}

Fogelman, Alan M. ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

[2] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA

[3] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90024 USA

[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA

[5] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA

[6] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA USA

[7] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Coll Letters & Sci, Los Angeles, CA USA

[10] Howard Hughes Med Inst, Los Angeles, CA USA

来源：

JOURNAL OF LIPID RESEARCH | 2017年 / 58卷 / 08期

关键词：

apolipoprotein A-I mimetic peptides; ather-osclerosis; hyperlipidemia; oxysterols; E-NULL MICE; LYSOPHOSPHATIDIC ACID; DENSITY-LIPOPROTEIN; SMALL-INTESTINE; ATHEROSCLEROSIS; TRANSPORT; D-4F; PHOSPHOLIPIDS; DYSLIPIDEMIA; INFLAMMATION;

D O I：

10.1194/jlr.M076554

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-beta in jejunum as determined by quantitative RT-PCR (RT-qPCR), immunohistochemistry (IHC), and ELISA (all P < 0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR (P < 0.0001), IHC (P = 0.0019), and ELISA (P < 0.0001), resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS (P < 0.0001). Adding ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0.06% by weight of diet substantially ameliorated these changes. Adding either ezetimibe or Tg6F to WD also ameliorated WD-induced changes in plasma lipids, serum amyloid A, and HDL cholesterol. Adding the same doses of ezetimibe and Tg6F together to WD (combined formulation) was generally more efficacious compared with adding either agent alone. Surprisingly, adding ezetimibe during the preparation of Tg6F, but before addition to WD, was more effective than the combined formulation for all parameters measured in jejunum (P = 0.0329 to P < 0.0001). We conclude the following: i) WD induces IFN-beta, CH25H, and 25-OHC in jejunum; and ii) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-beta, CH25H, and 25-OHC.

引用

页码：1636 / 1647

页数：12