title: Supplementation with linoleic acid-rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1-mediated triglyceride biosynthesis.
abstract: During the last decades there has been a staggering rise in human consumption of soybean oil (SO) and its major polyunsaturated fatty acid linoleic acid (LA). The role of SO or LA in cardiovascular diseases is highly controversial, and their impact on macrophage foam cell formation, the hallmark of early atherogenesis, is unclear. To investigate the effects of high SO or LA intake on macrophage lipid metabolism and the related mechanisms of action, C57BL/6 mice were orally supplemented with increasing levels of SO-based emulsion or equivalent levels of purified LA for 1 month, followed by analyses of lipid accumulation and peroxidation in aortas, serum and in peritoneal macrophages (MPM) of the mice. Lipid peroxidation and triglyceride mass in aortas from SO or LA supplemented mice were dose-dependently and significantly increased. In MPM from SO or LA supplemented mice, lipid peroxides were significantly increased and a marked accumulation of cellular triglycerides was found in accordance with enhanced triglyceride biosynthesis rate and overexpression of diacylglycerol acyltransferase1 (DGAT1), the key enzyme in triglyceride biosynthesis. In cultured J774A.1 macrophages treated with SO or LA, triglyceride accumulated via increased oxidative stress and a p38 mitogen-activated protein kinase (MAPK)-mediated overexpression of DGAT1. Accordingly, anti-oxidants (pomegranate polyphenols), inhibition of p38 MAPK (by SB202190) or DGAT1 (by oleanolic acid), all significantly attenuated SO or LA-induced macrophage triglyceride accumulation. These findings reveal novel mechanisms by which supplementation with SO or LA stimulate macrophage foam cell formation, suggesting a pro-atherogenic role for overconsumption of SO or LA. © 2016 BioFactors, 43(1):100-116, 2017.
authors: The Lipid Research Laboratory, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors: Oren
authors: O
authors: Rom
authors: The Lipid Research Laboratory, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.|Department of Internal Medicine E, Rambam Health Care Campus, Haifa, Israel.
authors: Helana
authors: H
authors: Jeries
authors: The Lipid Research Laboratory, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.|Department of Internal Medicine E, Rambam Health Care Campus, Haifa, Israel.
authors: Tony
authors: T
authors: Hayek
authors: The Lipid Research Laboratory, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors: Michael
authors: M
authors: Aviram
mesh_terms: D000818:Animals; D002460:Cell Line; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism*; D019587:Dietary Supplements; D004353:Drug Evaluation, Preclinical; D005487:Foam Cells / Q000187:drug effects / Q000502:physiology*; D019787:Linoleic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013024:Soybean Oil / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014280:Triglycerides; D013024:Soybean Oil; D019787:Linoleic Acid; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: linoleic acid; macrophage foam cells; oxidative stress; soybean oil; triglycerides