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D‐4F‐mediated reduction in metabolites of arachidonic and linoleic acids in the small intestine is associated with decreased inflammation in low‐density lipoprotein receptor‐null mice (LB708)
Author(s) -
Aram Negar,
Reddy Srinivasa,
Anantharamaiah G.,
Hough Greg,
Buga Georgette,
Danciger Jan,
Fogelman Alan,
Navab Mohamad
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb708
Subject(s) - medicine , endocrinology , arachidonic acid , small intestine , chemistry , ldl receptor , triglyceride , linoleic acid , oral administration , lipoprotein , inflammation , low density lipoprotein , cholesterol , receptor , biology , biochemistry , fatty acid , enzyme
Our group hypothesized that intestine is a major site of action for D‐4F, low‐density lipoprotein receptor null (LDLR) mice were fed a Western diet (WD) and administered the peptide subcutaneously (SQ) or orally. Plasma and liver D‐4F levels were 298‐fold and 96‐fold higher, respectively, after SQ administration, whereas D‐4F levels in small intestine were similar whether D‐4F was administered orally or SQ. Levels of metabolites of arachidonic and linoleic acids known to bind with high affinity to D‐4F were significantly reduced in intestine, liver and hepatic bile to a similar degree whether administered SQ or orally. However, levels of 20‐hydroxyeicosatetraenoic acid (HETE), which is known to bind the peptide with low affinity, were unchanged. D‐4F treatment reduced plasma serum amyloid A (SAA) and triglyceride levels and increased HDL‐cholesterol levels after SQ or oral administration. Plasma levels of metabolites of arachidonic and linoleic acids significantly correlated with SAA levels. Feeding 15‐HETE chow diet (without WD) significantly increased plasma SAA and triglyceride levels and decreased HDL‐cholesterol and paraoxonase activity, all of which were significantly enhanced by SQ D‐4F. Our group concludes that D‐4F administration reduces levels of free metabolites of arachidonic and linoleic acids in the small intestine and this is associated with decreased inflammation in LDLR null mice.