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Regulation of arginine metabolism by dietary fatty acids. Involvement of PPAR‐alpha
Author(s) -
Guelzim Najoua,
Mariotti Francois,
Lasserre Frederic,
Mathe Veronique,
Azzout Dalila,
Pineau Thierry,
Huneau JeanFrancois,
Hermier Dominique
Publication year - 2008
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.22.1_supplement.1093.7
Subject(s) - arginase , medicine , endocrinology , arginine , urea , chemistry , metabolism , nitric oxide , peroxisome proliferator activated receptor , nitric oxide synthase , amino acid , biochemistry , biology , receptor
Nitric oxide (NO) production depends on Arginine (Arg) competitive channelling towards urea ( via Arginase) vs NO ( via NO synthase, NOS). The regulation of these pathways by dietary PPARα ligands was explored in wild‐type (WT) and PPARα‐null (KO) male mice, fed diets rich in either saturated fatty acids (SFA) or 18:3 n‐3 (ALA). Metabolic markers of Arg metabolism were assayed in urine and plasma. Whole‐body NO production was assessed via the conversion of an IP bolus dose of [ 15 N 2 ‐guanido]‐arginine into urinary 15 NO 3 vs [ 15 N 2 ]‐urea. Enzymatic markers (protein and/or mRNA levels of Arginase and of endothelial and inducible NOS) were determined in liver. Diet effects in WT mice. In ALA‐fed mice, protein (Arginase) and mRNA (Arginase and both NOS) levels were half those in SFA‐fed mice. However, plasma urea and Arg, urine urea and nitrates, and whole‐body conversion of Arg into NO did not differ between diets. Effects of PPARα deficiency. In KO mice, Arginase protein and mRNA levels were half those in the WT groups, without effects on plasma and urinary metabolic markers, or on NOS expression. Besides, PPARα invalidation tended to reduce the dietary effects. However, the whole‐body conversion of Arg into NO tended to be lower (by 50%) in KO mice fed ALA than in those fed SFA. Conclusion. In this model, the nature of dietary fatty acids (SFA vs ALA) impacts Arg metabolic pathways, of which regulation might be mediated in part by PPARα.