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Mol Nutr Food Res. 2016 Oct;60(10):2208-2218. doi: 10.1002/mnfr.201600142. Epub 2016 Jul 12.

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

Author information

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.

KEYWORDS:

Atherosclerosis; Cholesterol efflux; Inflammation; Long-chain monounsaturated fatty acids; PPAR signaling pathway

PMID:
27273599
PMCID:
PMC5056854
DOI:
10.1002/mnfr.201600142
[Indexed for MEDLINE]
Free PMC Article

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