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

Pallavi Mukherjee, Greg Hough, Arnab Chattopadhyay, Mohamad Navab, Hannah R. Fogelman, David Meriwether, Kevin Williams, Steven Bensinger, Travis Moller, Kym F. Faull, Aldons J. Lusis, M. Luisa Iruela-Arispe, Kristina I. Bostrom, Peter Tontonoz, Srinivasa T. Reddy*, Alan M. Fogelman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1636-1647
Number of pages12
JournalJournal of lipid research
Volume58
Issue number8
DOIs
StatePublished - Aug 1 2017

Keywords

  • Apolipoprotein A-I mimetic peptides
  • Atherosclerosis
  • Hyperlipidemia
  • Oxysterols

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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