title: NO synthesis from arginine is favored by α-linolenic acid in mice fed a high-fat diet.
abstract: Alterations in NO availability and signaling play a pivotal role at early stages of the metabolic syndrome (MetSynd). We hypothesized that dietary α-linolenic acid (ALA, 18:3 n-3) favors NO availability by modulating amino acid metabolism, with a specific impact on the arginine-NO pathway. Mice were fed a hyperlipidic diet (285 g lipid/kg, 51.1 % energy), rich in either saturated fatty acids (SFA, provided by palm oil, PALM group) or ALA (provided by linseed oil, LIN group). We measured whole-body NO synthesis and systemic arginine hydrolysis with a tracer-based method, plasma concentration of related metabolites, and hepatic mRNA level of related enzymes, and the study was completed by a transcriptomic analysis in the liver. As expected with this model, hyperlipidic diets resulted in increased adiposity and glycemia after 5 weeks. As compared to PALM mice, LIN mice had a higher plasma nitrite and nitrate concentration, a higher whole-body conversion of arginine into NO vs urea, and a similar plasma concentration of asymmetric dimethylarginine (ADMA), despite a higher expression of the liver dimethylargininase-1. In LIN mice, there was a higher expression of genes involved in PPARα signaling, but a little impact on gene expression related to amino acids and arginine metabolism. This effect cannot be directly ascribed to changes in arginase activity in the liver or ADMA metabolism, nor to direct regulation of the related target genes. In conclusion, dietary ALA favors NO synthesis, which could contribute to rescue NO availability when jeopardized by the nutritional conditions in relation with the initiation of the MetSynd.
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France. dominique.hermier@agroparistech.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Hermier
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France.
authors.forename: Najoua
authors.initials: N
authors.lastname: Guelzim
authors.affiliation: UMR ToxAlim, INP, INRA, Université de Toulouse, 31027, Toulouse, France.
authors.forename: Pascal G P
authors.initials: PG
authors.lastname: Martin
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Huneau
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathé
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Quignard-Boulangé
authors.affiliation: UMR ToxAlim, INP, INRA, Université de Toulouse, 31027, Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lasserre
authors.affiliation: UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, 75005, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Mariotti
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000097:blood*; D047493:PPAR alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D047493:PPAR alpha; D017962:alpha-Linolenic Acid; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: Amino acids; Arginine; Metabolic syndrome; n-3 PUFA; α-Linolenic acid