Trimethylamine N-oxide attenuates high-fat high-cholesterol dietinduced steatohepatitis by reducing hepatic cholesterol overload in rats |
| |
Authors: | Ze-Hua Zhao Feng-Zhi Xin Da Zhou Ya-Qian Xue Xiao-Lin Liu Rui-Xu Yang Qin Pan Jian-Gao Fan |
| |
Institution: | Center for Fatty Liver;CAS Key Laboratory of Nutrition;Shanghai Key Lab of Pediatric Gastroenterology and Nutrition |
| |
Abstract: | BACKGROUND Trimethylamine N-oxide(TMAO) has been shown to be involved in cardiovascular disease(CVD). However, its role in nonalcoholic steatohepatitis(NASH) is unknown.AIM To determine the effect of TMAO on the progression of NASH.METHODS A rat model was induced by 16-wk high-fat high-cholesterol(HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk.RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats.Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum(ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased byTMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora.CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment. |
| |
Keywords: | Gut microbiota Trimethylamine N-oxide Nonalcoholic steatohepatitis Endoplasmic reticulum stress Cholesterol |
本文献已被 CNKI 维普 等数据库收录! |
| 点击此处可从《世界胃肠病学杂志(英文版)》浏览原始摘要信息 |