title: Generation and esterification of electrophilic fatty acid nitroalkenes in triacylglycerides.
abstract: Electrophilic fatty acid nitroalkenes (NO(2)-FA) are products of nitric oxide and nitrite-mediated unsaturated fatty acid nitration. These electrophilic products induce pleiotropic signaling actions that modulate metabolic and inflammatory responses in cell and animal models. The metabolism of NO(2)-FA includes reduction of the vinyl nitro moiety by prostaglandin reductase-1, mitochondrial β-oxidation, and Michael addition with low molecular weight nucleophilic amino acids. Complex lipid reactions of fatty acid nitroalkenes are not well defined. Herein we report the detection and characterization of NO(2)-FA-containing triacylglycerides (NO(2)-FA-TAG) via mass spectrometry-based methods. In this regard, unsaturated fatty acids of dietary triacylglycerides are targets for nitration reactions during gastric acidification, where NO(2)-FA-TAG can be detected in rat plasma after oral administration of nitro-oleic acid (NO(2)-OA). Furthermore, the characterization and profiling of these species, including the generation of beta oxidation and dehydrogenation products, could be detected in NO(2)-OA-supplemented adipocytes. These data revealed that NO(2)-FA-TAG, formed by either the direct nitration of esterified unsaturated fatty acids or the incorporation of nitrated free fatty acids into triacylglycerides, contribute to the systemic distribution of these reactive electrophilic mediators and may serve as a depot for subsequent mobilization by lipases to in turn impact adipocyte homeostasis and tissue signaling events.
authors.affiliation: Fondazione Ri.MED, Via Bandiera 11, 90133 Palermo, Italy; Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Fazzari
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Khoo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Woodcock
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA. Electronic address: freerad@pitt.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, 15261 PA, USA. Electronic address: fjs2@pitt.edu.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Schopfer
mesh_terms: D000475:Alkenes / Q000378:metabolism*; D000818:Animals; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009574:Nitro Compounds / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000475:Alkenes; D005227:Fatty Acids; D009574:Nitro Compounds; D014280:Triglycerides; D009569:Nitric Oxide; D044925:Oxidoreductases Acting on CH-CH Group Donors
keywords: Adipocytes; Conjugated linoleic acid; Nitrate; Nitrite; Nitro fatty acids; Nitro-oleic acid; Nitroalkane; Triglycerides