Premium
Nitro‐Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes
Author(s) -
Rosenblat Mira,
Rom Oren,
Volkova Nina,
Aviram Michael
Publication year - 2016
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-016-4169-2
Subject(s) - triglyceride , chemistry , oleic acid , biochemistry , cholesterol , reactive oxygen species , lipid metabolism , medicine , lipoprotein lipase , endocrinology , adipose tissue , biology
Nitro‐fatty acids possess anti‐atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro‐oleic acid (OLA‐NO 2 ) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti‐oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA‐NO 2 (0–1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7‐dichlorofluorescein diacetate, decreased dose‐dependently, but the anti‐oxidative effects of OLA‐NO 2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA‐NO 2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA‐NO 2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA‐NO 2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA‐NO 2 treated cells demonstrated down‐regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone‐sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA‐NO 2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein‐mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA‐NO 2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti‐oxidants and triglyceride metabolizing enzymes.