Plasma trimethylamine-N-oxide (TMAO) is a risk factor for development of atherosclerosis in humans. It is known that that consumption of ω-3 polyunsaturated fatty acids (PUFAs) is beneficial to cardiovascular health. The present study was to compare the protective effects of flaxseed oil rich in α-linolenic acid (ALA, 18:3n-3), and fish oil rich in eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in TMAO-exacerbated atherosclerosis in mice. Forty-five male ApoE<sup>-/-</sup> mice were randomly divided into five groups and fed a low-fat diet (LFD), a western diet (WD), a WD plus 0.2% TMAO (WD+TMAO), or one of two experimental TMAO-containing WDs with half of lard substituted by flaxseed oil (FLO+TMAO) or fish oil (FIO+TMAO), respectively. After 12-week feeding, results showed that 0.2% dietary TMAO raised plasma TMAO concentration by approximate three folds compared to WD, accompanied by elevated plasma levels of pro-inflammatory cytokines, disturbance in cholesterol homeostasis, and more severe atherosclerotic plaque formation. Compared to flaxseed oil, fish oil showed more potent activity to lower plasma levels of total cholesterol (T-C) and pro-inflammatory cytokines, leading to a larger reduction in atherosclerotic plaque area. Both oils were able to reverse the TMAO-induced declines in excretion of fecal acidic sterols via up-regulating the expression of hepatic cholesterol 7α-hydroxylase (CYP7A1). In addition, fish oil promoted the fecal output of neutral sterols and down-regluated the expression of hepatic cholesterol synthesis by hepatic down-regulating 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), contributing to its more effective cholesterol-lowering capacity. The 16S rRNA analysis revealed that fish oil but not flaxseed oil decreased the ratio of Firmicutes to Bacteroidetes. Both oils raised the abundance of short-chain fatty acid (SCFA)-producing bacteria in mice, leading to a higher microbial generation of SCFA. It was concluded that fish oil was more effective than flaxseed oil in ameliorating the TMAO-exacerbated atherogenesis at least in ApoE<sup>-/-</sup> mice.

Protective effects of flaxseed oil and fish oil on TMAO-exacerbated atherogenesis

2019 Fall National Meeting

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