Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models

• Published in: Molecular nutrition & food research 2016-10, Vol.60 (10), p.2208-2218
• Main Authors: Yang, Zhi-Hong, Bando, Masahiro, Sakurai, Toshihiro, Chen, Ye, Emma-Okon, Beatrice, Wilhite, Bree, Fukuda, Daiju, Vaisman, Boris, Pryor, Milton, Wakabayashi, Yoshiyuki, Sampson, Maureen, Yu, Zu-Xi, Sakurai, Akiko, Zarzour, Abdalrahman, Miyahara, Hiroko, Takeo, Jiro, Sakaue, Hiroshi, Sata, Masataka, Remaley, Alan T.
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Cell Line; Cholesterol - metabolism; Cholesterol efflux; Cytokines - blood; Disease Models, Animal; Fatty Acids - analysis; Fatty Acids, Monounsaturated - chemistry; Fatty Acids, Monounsaturated - pharmacology; Fish Oils - chemistry; Fish Oils - pharmacology; Humans; Inflammation; Lipids - blood; Liver - drug effects; Liver - metabolism; Liver - physiology; Long-chain monounsaturated fatty acids; Macrophages - drug effects; Macrophages - metabolism; Mice, Knockout; PPAR signaling pathway; Receptors, LDL - genetics
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201600142

Scope 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. Methods and results 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. Conclusion Our research showed for the first time that LCMUFA consumption protects against diet‐induced atherosclerosis, possibly by upregulating the PPAR signaling pathway. To investigate the effect of long‐chain monounsaturated fatty acid (LCMUFA) at least 20 carbons in length (i.e., C20:1 and C22:1 isomers combined) on atherosclerosis, a major cause of cardiovascular disease, two types of atherosclerotic mouse models were fed with LCMUFA‐rich diet for three months. In ApoE‐KO mice, 5% LCMUFA‐supplemented diet decreased plasma cholesterol, and suppressed atherosclerosis. In LDLR‐KO mice, a lower dose 2% LCMUFA also suppressed atherosclerosis and macrophage accumulation at aorta, although shorter‐chain MUFA oleic acid (C18:1)‐rich olive oil did not.