Zhi-Hong Yang1, Masahiro Bando2, Toshihiro Sakurai3, Ye Chen4, Beatrice Emma-Okon3, Bree Wilhite5, Daiju Fukuda2, Boris Vaisman3, Milton Pryor3, Yoshiyuki Wakabayashi6, Maureen Sampson7, Zu-Xi Yu8, Akiko Sakurai3, Abdalrahman Zarzour3, Hiroko Miyahara9, Jiro Takeo9, Hiroshi Sakaue2, Masataka Sata2, Alan T Remaley3. 1. 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. 2. Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. 3. Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA. 4. Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA. 5. Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA. 6. DNA Sequencing Core, NHLBI, NIH, Bethesda, MD, USA. 7. Clinical Center, Department of Laboratory Medicine, NIH, Bethesda, MD, USA. 8. Pathology Core, NHLBI, NIH, Bethesda, MD, USA. 9. Central Research Laboratory, Nippon Suisan Kaisha, Tokyo, Japan.
Abstract
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.
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, oliveoil, or not (control) for 12 wk. LCMUFA, but not oliveoil, 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.
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