| Summary: | 碩士 === 國立臺灣大學 === 食品科技研究所 === 107 === Cardiovascular disease (CVD) has become a ubiquitous cause of morbidity and a leading contributor to mortality in most countries. Atherosclerosis, a major component of CVD, has properly been considered a public health problem of industrialized countries. Trimethylamine-N-oxide (TMAO) was recently discovered as a proatherogenic species which is generated from dietary carnitine through gut microbiota-dependent pathway. Carnitine, a dietary quaternary amine, has been identified to specifically metabolize to trimethylamine (TMA) by gut microbiota and subsequently oxidize to TMAO by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of dietary phenolic compounds (pterostilbene, oolong tea extract and polymethoxyflavones mixture) on reducing TMAO formation and on reversing vascular inflammation in carnitine-feeding mice. Our studies used LC-MS/MS to detect plasma TMAO and the results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group; and these three phenolic compounds can reverse it. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, these dietary compounds decreased mRNA levels of vascular inflammatory markers (TNF-α, VCAM-1 and E-selectin). We analyzed the taxonomic compositions of the microbiota using 16S rRNA gene sequencing of DNA extracted from the cecal samples. It has been found that these three dietary compounds can modulate the growth of certain gut microbiota in vivo. Genus-level analysis showed that these three dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to carnitine only group. Administration of polymethoxyflavones mixture increased Akkermansia in mice. In conclusion, pterostilbene, oolong tea extract and polymethoxyflavones have protective effects against carnitine feeding-induced vascular inflammation by gut microbiota remodeling and decreased TMAO levels through hepatic FMO3 mRNA reduction.
|
|---|
