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J Lipid Res. 2017 Aug;58(8):1636-1647. doi: 10.1194/jlr.M076554. Epub 2017 Jun 7.

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

Author information

1
Departments of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
2
Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
3
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, CA.
4
Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
5
Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA.
6
Department of Molecular, Cell, and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, CA.
7
Howard Hughes Medical Institute, Los Angeles, CA.
8
Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
9
Departments of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA sreddy@mednet.ucla.edu.
10
Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Abstract

Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-β 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-β, CH25H, and 25-OHC in jejunum; and ii) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-β, CH25H, and 25-OHC.

KEYWORDS:

apolipoprotein A-I mimetic peptides; ather­osclerosis; hyperlipidemia; oxysterols

PMID:
28592401
PMCID:
PMC5538285
DOI:
10.1194/jlr.M076554
[Indexed for MEDLINE]
Free PMC Article

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