Numerous studies have shown cardiovascular benefits of fish oil, and most of these favorable effects have been attributed to omega-3 fatty acids. Fish oils, however, also contain varying amounts of other unusual types of fatty acids, such as long-chain monounsaturated fatty acids (LCMUFA; i.e., C20:1 and C22:1 isomers combined). Compared with well-studied omega-3, limited information is available on the role of LCMUFA on cardiovascular disease. In the current study, we examined the effect of saury fish oil-derived LCMUFA concentrate on the pathogenesis of atherosclerosis in ApoE-deficient and LDLR-deficient mice. Male ApoE-deficient mice were fed a western diet supplemented with 5% LCMUFA concentrate or not (control) for 12 weeks.
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Sudan IV staining of the aorta revealed that LCMUFA significantly suppressed the development of atherosclerotic lesions, and down-regulated inflammatory gene expression. In LDLR-deficient female mice, we also observed that 12-week supplementation of 2% LCMUFA on a western diet significantly decreased atherosclerosis lesion areas and accumulation of macrophages, compared with western diet (control) or western diet supplemented with 2% olive oil enriched in shorter-chain MUFA oleic acid (C18:1). There were no differences, however, in plasma or hepatic lipid profiles between the three groups. LCMUFA, but not olive oil, also significantly suppressed several plasma inflammatory cytokine levels. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from the LCMUFA group promoted cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. LCMUFA also suppressed LPS-induced inflammatory cytokine production by macrophages. In conclusion, our research showed for the first time that LCMUFA consumption could protects against atherosclerosis, possibly by upregulating the PPAR signaling pathway. Omega-3 fatty acids are generally considered the major active components in fish lipids, but our findings provide new insights into potential health effect of LCMUFA-rich fish oil and suggest that LCMUFA-rich fish oil may also be beneficial for reducing cardiovascular disease risk.
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