Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Instituto de Investigación en Ciencias de la Alimentación (CSIC-UAM), Nicolás Cabrera 9, Campus de Cantoblanco, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Food Chem. 2024 Mar 30;437(Pt 1):137767. doi: 10.1016/j.foodchem.2023.137767. Epub 2023 Oct 14.
Nitrated fatty acids are important anti-inflammatory and protective lipids formed in the gastric compartment, with conjugated linoleic acid (rumenic acid, RA, 9Z,11E-18:2) being the primary substrate for lipid nitration. The recently reported identification of nitrated rumelenic acid (NO-RLA) in human urine has led to hypothesize that rumelenic acid (RLA, 9Z,11E,15Z-18:3) from dairy fat is responsible for the formation of NO-RLA. To evaluate the source and mechanism of NO-RLA formation, N labeled standards of NO-RLA were synthesized and characterized. Afterward, milk fat with different RA and RLA levels was administered to mice in the presence of nitrite, and the appearance of nitrated fatty acids in plasma and urine followed. We confirmed the formation of NO-RLA and defined the main metabolites in plasma, urine, and tissues. In conclusion, RLA obtained from dairy products is the main substrate for forming this novel electrophilic lipid reported to be present in human urine.
硝代脂肪酸是胃腔中形成的重要抗炎和保护脂质,共轭亚油酸(反式 9,11-十八碳二烯酸,RA,9Z,11E-18:2)是脂质硝化的主要底物。最近在人尿中发现的硝代rumelenic 酸(NO-RLA)的报道使人们假设来自乳脂的 rumelenic 酸(RLA,9Z,11E,15Z-18:3)是形成 NO-RLA 的原因。为了评估 NO-RLA 形成的来源和机制,合成并表征了 N 标记的 NO-RLA 标准品。此后,在存在亚硝酸盐的情况下向小鼠给予具有不同 RA 和 RLA 水平的乳脂肪,并检测血浆和尿液中硝代脂肪酸的出现情况。我们证实了 NO-RLA 的形成,并确定了在血浆、尿液和组织中主要的代谢物。总之,乳制品中的 RLA 是形成这种新型亲电脂质的主要底物,据报道该脂质存在于人尿中。