Long-Chain Monounsaturated Fatty Acids Improve Endothelial Function with Altering Microbial Flora

Abstract

Background: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFAs) with a carbon chain length longer than 18 units ameliorate cardiovascular risk factors in mice. In this study, we investigated whether LCMUFAs could improve endothelial functions in mice and humans. Methods: In a double-blind randomised placebo-controlled, parallel-group, multi-centre 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, Apo-E−/− mice were fed a Western diet supplemented with 3% of either C20:1 or C22:1 fatty acids for 12 weeks. Findings: Participants from the LCMUFA group showed improvements in endothelial function, an increased GLP-1 level, and lower trimethylamine-N-oxide level, which is a predictor of coronary artery disease. C20:1 and C22:1 oils significantly improved atherosclerotic lesions and several plasma inflammatory cytokine levels including IL-6 and TNF-α. These beneficial effects were consistent with an improvement in the gut microbiota environment, as evident from the altered ratio of Firmicutes/Bacteroides, increase in the abundance of Akkermansia, and upregulation of short-chain fatty acid (SCFA)-induced glucagon-like peptide-1 (GLP-1) expression. Interpretation: These data suggest that LCMUFAs alter the microbiota environment that stimulates the production of SCFAs, which results in the induction of GLP-1 secretion. Fish oil-derived long-chain monounsaturated fatty acids might thus help to protect against cardiovascular disease. Trial Registration: This trial was registered at UMIN Clinical Trials Registry (registration number: UMI29181). Funding Statement: This study was supported by JSPS KAKENHI, grant number 19H04055, and the Agriculture, Forestry and Fisheries Research Council, grant 27016A. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This trial was approved by the Committee for Medical Ethics at Tokushima University Hospital, Tokushima, Japan (approval number: 3047). Written informed consent based on the Declaration of Helsinki was obtained from all participants.