Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models.
Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models.



LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells.



Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway.
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA. zhihong.yang@nih.gov.
Zhi-Hong
ZH
Yang
Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Masahiro
M
Bando
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Toshihiro
T
Sakurai
Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA.
Ye
Y
Chen
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Beatrice
B
Emma-Okon
Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Bree
B
Wilhite
Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Daiju
D
Fukuda
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Boris
B
Vaisman
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Milton
M
Pryor
DNA Sequencing Core, NHLBI, NIH, Bethesda, MD, USA.
Yoshiyuki
Y
Wakabayashi
Clinical Center, Department of Laboratory Medicine, NIH, Bethesda, MD, USA.
Maureen
M
Sampson
Pathology Core, NHLBI, NIH, Bethesda, MD, USA.
Zu-Xi
ZX
Yu
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Akiko
A
Sakurai
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Abdalrahman
A
Zarzour
Central Research Laboratory, Nippon Suisan Kaisha, Tokyo, Japan.
Hiroko
H
Miyahara
Central Research Laboratory, Nippon Suisan Kaisha, Tokyo, Japan.
Jiro
J
Takeo
Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Hiroshi
H
Sakaue
Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Masataka
M
Sata
Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Alan T
AT
Remaley
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D005395:Fish Oils / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics
D001057:Apolipoproteins E; D016207:Cytokines; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005395:Fish Oils; D008055:Lipids; D011973:Receptors, LDL; D002784:Cholesterol
Atherosclerosis; Cholesterol efflux; Inflammation; Long-chain monounsaturated fatty acids; PPAR signaling pathway