Long-chain monounsaturated fatty acids improve endothelial function with altering microbial flora

Yousuke Tanba,Daiju Fukuda,Ryoko Yoshimoto,Hiroshi Sakaue,Hiroko Miyahara,Masashi Kuroda,Yasuo M Tsutsumi,Nagakatsu Harada,Masataka Sata,Yuna Mishima,Nanako Ueshima,Rie Tsutsumi,Saeko Masumoto,Kana Takeji,Jiro Takeo,Mayu Sebe,Yuki Yamasaki,Masahiro Bando,Ken-Ichi Aihara

doi:10.1016/j.trsl.2021.03.016

Abstract

Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. In a double-blind, randomized, placebo-controlled, parallel-group, multi-center study, healthy subjects were randomly assigned to either an LCMUFA oil (saury oil) or a control oil (olive and tuna oils) group. Sixty subjects were enrolled and administrated each oil for 4 weeks. For the animal study, ApoE-/- mice were fed a Western diet supplemented with 3% of either gadoleic acid (C20:1) or cetoleic acid (C22:1) for 12 weeks. Participants from the LCMUFA group showed improvements in endothelial function and a lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and plasma levels of several inflammatory cytokines, including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the decreased ratio of Firmicutes and/ or Bacteroidetes, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression and serum GLP-1 level. These data suggest that LCMUFAs alter the microbiota environment that stimulate the production of SCFAs, resulting in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease.

Highlights

Cardiovascular disease (CVD) is the leading cause of mortality and disability worldwide.[1]
We set up an long-chain monounsaturated fatty acids (LCMUFAs) group fed with saury oil containing LCMUFAs, mainly C20:1 and C22:1 as well as eicosapentaenoic acid (EPA), and a control group treated with a mixture of olive oil and tuna oils
We investigated the level of GLP-1, which is associated with increased Short-chain fatty acids (SCFAs), and found it to be altered following LCMUFA treatment

Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality and disability worldwide.[1]. FMD, assessed by percent change of brachial artery flow-mediated dilatation after avascularization using ultrasonography, reflects endothelium-dependent and largely NO-mediated arterial function and has been widely recognized as an early surrogate marker for vascular health and CVD.[9]. Fish oil from saury is enriched in long-chain monounsaturated fatty acids (LCMUFAs) with at least 20-carbon-long chains (C20 and C22 isomers combined). We have previously shown that saury oil-derived LCMUFAs attenuate atherosclerosis development in ApoEÀ/À and LDLRÀ/À mice

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