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

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. Conclusions Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway.

Dietary marine-derived long-chain monounsaturated fatty acids and cardiovascular disease risk: a mini review

“…Interestingly, intake of LCMUFA concentrate has been shown to increase plasma/hepatic EPA and DHA levels and decrease arachidonic acid (C20:4 n-6) levels, although there were only trace levels of long-chain n-3 PUFA in the LCMUFA concentrate oil (EPA and DHA <0.5%) [42, 43, 46]. Mobilization of PUFA after LCMUFA diet feeding was also observed by Halvorsen et al [48].…”

“…The LCMUFA-induced improvements in diabetes may, therefore, be possibly related to the upregulation of Pparg and its target genes. Upregulation of PPAR family genes by dietary LCMUFA was also observed in ApoE-deficient mice and LDLR-deficient mice [46]. Both a higher dose 5% ( w/w ) or a lower dose 2% ( w/w ) LCMUFA supplementation in western diet significantly suppressed atherosclerotic development and upregulated key gene expression in PPAR signaling pathway, such as Pparα and Pparγ .…”

Effect of Dietary Components from Antarctic Krill on Atherosclerosis in apoE‐Deficient Mice

“…A less evident result was observed at the aortic sinus, where significance was reached only in the KRILL OIL group versus CONTROL. A moderate effect of the treatments at the aortic sinus was somehow expected, based on previous studies in similar animal models showing a higher susceptibility of the aorta compared to the aortic sinus to dietary treatments . The histological analysis of the aortic sinus was mainly conducted to assess if the different diets could affect atherosclerotic plaque composition.…”

Dietary α‐cyclodextrin reduces atherosclerosis and modifies gut flora in apolipoprotein E‐deficient mice

“…In humans, it is well known that serum lipids only account for about half of the variation in the propensity of atherosclerosis . In mouse models of atherosclerosis, other types of treatment, such as inulin , blueberries , long‐chain monounsaturated fatty acid‐rich fish oil , and the angiotensin II type 1 receptor blocker telmisartan all demonstrated decreased atherosclerotic lesions despite the absence of major effect on plasma lipids. Most relevant for this study, high fat diets supplemented with 10% oligofructose‐enriched inulin diminished the development of atherosclerosis in apoE‐KO mice, with an increase in cecal fermentation, despite minimal reductions of plasma TC and TG .…”