Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Arnab Chattopadhyay; Mohamad Navab; Greg Hough; Victor Grijalva; Pallavi Mukherjee; Hannah R Fogelman; Lin H Hwang; Kym F Faull; Aldons J Lusis; Srinivasa T Reddy; Alan M Fogelman

doi:10.1194/jlr.M064352

Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

J Lipid Res. 2016 May;57(5):832-47. doi: 10.1194/jlr.M064352. Epub 2016 Mar 9.

Affiliations

¹ Departments of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736.
² Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736.
³ Departments of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736 Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736 Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736.
⁴ Departments of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736 Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736 Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095-1736 [email protected].

Abstract

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.

Keywords: E06 antibody; Western diet; apolipoprotein A-I mimetic peptides; atherosclerosis; lysophosphatidic acid; lysophosphatidylcholine; transgenic tomatoes expressing the 6F peptide.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Diet, Western / adverse effects*
Dyslipidemias / blood
Dyslipidemias / drug therapy
Dyslipidemias / etiology
Enterocytes / metabolism
Female
Jejunum / drug effects
Jejunum / metabolism*
Lysophosphatidylcholines / adverse effects*
Lysophosphatidylcholines / blood
Mice, Inbred C57BL
Mice, Knockout
Oxidation-Reduction
Peptides / administration & dosage*
Phospholipids / metabolism*
Plants, Genetically Modified / chemistry
Plants, Genetically Modified / genetics
Receptors, LDL / genetics
Solanum lycopersicum / chemistry
Solanum lycopersicum / genetics

Substances

6F peptide
Lysophosphatidylcholines
Peptides
Phospholipids
Receptors, LDL

Grants and funding

P01 HL030568/HL/NHLBI NIH HHS/United States