TY - JOUR
T1 - Dietary supplementation with long-chain monounsaturated fatty acid isomers decreases atherosclerosis and alters lipoprotein proteomes in LDLr−/− mice
AU - Yang, Zhi Hong
AU - Gordon, Scott M.
AU - Sviridov, Denis
AU - Wang, Shuibang
AU - Danner, Robert L.
AU - Pryor, Milton
AU - Vaisman, Boris
AU - Shichijo, Yuka
AU - Doisaki, Nobushige
AU - Remaley, Alan T.
N1 - Publisher Copyright:
© 2017
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Background and aims Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models. It is not clear, however, how individual LCMUFA isomers may act on atherosclerosis. Methods In the present study, we used saury fish oil-derived concentrates enriched in either C20:1 or C22:1 isomer fractions to investigate their individual effect on atherosclerosis and lipoprotein metabolism. LDLR-deficient (LDLr−/−) mice were fed a Western diet supplemented with 5% (w/w) of either C20:1 or C22:1 concentrate for 12 wk. Results Compared to the control Western diet with no supplement, both LCMUFA isomers increased hepatic levels of LCMUFA by 2∼3-fold (p < 0.05), and decreased atherosclerotic lesion areas by more than 40% (p < 0.05), although there were no major differences in plasma lipoproteins or hepatic lipid content. Both LCMUFA isomers significantly decreased plasma CRP levels, improved Abca1-dependent cholesterol efflux capacity of apoB-depleted plasma, and enhanced Ppar transcriptional activities in HepG2 cells. LC-MS/MS proteomic analysis of lipoproteins (HDL, LDL and VLDL) revealed that both LCMUFA isomer diets resulted in similar potentially beneficial alterations in proteins involved in complement activation, blood coagulation, and lipid metabolism. Several lipoprotein proteome changes were significantly correlated with atherosclerotic plaque reduction. Conclusions Dietary supplementation with the LCMUFA isomers C20:1 or C22:1 was equally effective in reducing atherosclerosis in LDLr−/−mice and this may partly occur through activation of the Ppar signaling pathways and favorable alterations in the proteome of lipoproteins.
AB - Background and aims Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models. It is not clear, however, how individual LCMUFA isomers may act on atherosclerosis. Methods In the present study, we used saury fish oil-derived concentrates enriched in either C20:1 or C22:1 isomer fractions to investigate their individual effect on atherosclerosis and lipoprotein metabolism. LDLR-deficient (LDLr−/−) mice were fed a Western diet supplemented with 5% (w/w) of either C20:1 or C22:1 concentrate for 12 wk. Results Compared to the control Western diet with no supplement, both LCMUFA isomers increased hepatic levels of LCMUFA by 2∼3-fold (p < 0.05), and decreased atherosclerotic lesion areas by more than 40% (p < 0.05), although there were no major differences in plasma lipoproteins or hepatic lipid content. Both LCMUFA isomers significantly decreased plasma CRP levels, improved Abca1-dependent cholesterol efflux capacity of apoB-depleted plasma, and enhanced Ppar transcriptional activities in HepG2 cells. LC-MS/MS proteomic analysis of lipoproteins (HDL, LDL and VLDL) revealed that both LCMUFA isomer diets resulted in similar potentially beneficial alterations in proteins involved in complement activation, blood coagulation, and lipid metabolism. Several lipoprotein proteome changes were significantly correlated with atherosclerotic plaque reduction. Conclusions Dietary supplementation with the LCMUFA isomers C20:1 or C22:1 was equally effective in reducing atherosclerosis in LDLr−/−mice and this may partly occur through activation of the Ppar signaling pathways and favorable alterations in the proteome of lipoproteins.
KW - Atherosclerosis
KW - Cholesterol efflux
KW - Inflammation
KW - Lipoprotein proteome
KW - Long-chain monounsaturated fatty acids
KW - Peroxisome proliferator-activated receptors
UR - http://www.scopus.com/inward/record.url?scp=85018784783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018784783&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2017.04.017
DO - 10.1016/j.atherosclerosis.2017.04.017
M3 - Article
C2 - 28486149
AN - SCOPUS:85018784783
SN - 0021-9150
VL - 262
SP - 31
EP - 38
JO - Atherosclerosis
JF - Atherosclerosis
ER -