Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, Unites States.
Department of Pediatrics, University of California San Diego, La Jolla, CA, Unites States; Klinik und Poliklinik für Kardiologie, University Hospital Leipzig, Leipzig University, Germany.
Prostaglandins Leukot Essent Fatty Acids. 2021 Sep;172:102316. doi: 10.1016/j.plefa.2021.102316. Epub 2021 Jun 24.
The oxidation of dietary linoleic acid (LA) produces oxidized LA metabolites (OXLAMs) known to regulate multiple signaling pathways in vivo. Recently, we reported that feeding OXLAMs to mice resulted in liver inflammation and apoptosis. However, it is not known whether this is due to a direct effect of OXLAMs accumulating in the liver, or to their degradation into bioactive shorter chain molecules (e.g. aldehydes) that can provoke inflammation and related cascades. To address this question, mice were fed a low or high LA diet low in OXLAMs, or a low LA diet supplemented with OXLAMs from heated corn oil (high OXLAM diet). Unesterified oxidized fatty acids (i.e. oxylipins), including OXLAMs, were measured in liver after 8 weeks of dietary intervention using ultra-high pressure liquid chromatography coupled to tandem mass-spectrometry. The high OXLAM diet did not alter liver oxylipin concentrations compared to the low LA diet low in OXLAMs. Significant increases in several omega-6 derived oxylipins and reductions in omega-3 derived oxylipins were observed in the high LA dietary group compared to the low LA group. Our findings suggest that dietary OXLAMs do not accumulate in liver, and likely exert pro-inflammatory and pro-apoptotic effects via downstream secondary metabolites.
膳食亚油酸（LA）的氧化会产生氧化的 LA 代谢物（OXLAMs），已知这些代谢物可调节体内的多种信号通路。最近，我们报道了给小鼠喂食 OXLAMs 会导致肝脏炎症和细胞凋亡。然而，目前尚不清楚这是由于 OXLAMs 在肝脏中积累而直接导致的，还是由于它们降解成具有生物活性的短链分子（例如醛）而引发炎症和相关级联反应。为了解决这个问题，我们用低 OXLAMs 的低 LA 饮食或富含 OXLAMs 的加热玉米油（高 OXLAM 饮食）来喂养小鼠。使用超高效液相色谱-串联质谱法在 8 周的饮食干预后测量肝脏中的未酯化氧化脂肪酸（即 oxylipins），包括 OXLAMs。与低 LA 低 OXLAMs 饮食相比，高 OXLAM 饮食并未改变肝脏 oxylipin 浓度。与低 LA 组相比，高 LA 饮食组中几种 omega-6 衍生的 oxylipin 显著增加，而 omega-3 衍生的 oxylipin 减少。我们的研究结果表明，膳食 OXLAMs 不会在肝脏中积累，并且可能通过下游次级代谢物发挥促炎和促凋亡作用。
