Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid

Mohamad Navab, Greg Hough, Georgette M. Buga, Feng Su, Alan C. Wagner, David Meriwether, Arnab Chattopadhyay, Feng Gao, Victor Grijalva, Janet S. Danciger, Brian J. Van Lenten, Elin Org, Aldons J. Lusis, Calvin Pan, G. M. Anantharamaiah, Robin Farias-Eisner, Susan S. Smyth, Srinivasa T. Reddy, Alan M. Fogelman

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR-/-) mice fed a Western diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in the small intestine of LDLR mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by quantitative RT-PCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i) levels of LPA in the small intestine were similar to those induced by feeding WD; ii) gene expression changes in the small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL-cholesterol levels, and the fast-performance liquid chromatography lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes.

Original languageEnglish
Pages (from-to)3403-3418
Number of pages16
JournalJournal of Lipid Research
Volume54
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • 6F peptide
  • Apolipoprotein A-I mimetic peptides
  • Atherosclerosis
  • Genetically engineered tomato plants
  • Lysophosphatidic acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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