Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice

文献类型： 外文期刊

第一作者： Zhu, Ru-Gang

作者： Zhu, Ru-Gang;Sun, Yan-Di;Hou, Yu-Ting;Li, Tuo-Ping;Fan, Jun-Gang;Chen, Gang

作者机构：

关键词： Haw pectin penta-oligogalacturonide; Cholesterol accumulation; Bile acids synthesis; Transport; Excretion

期刊名称：CHEMICO-BIOLOGICAL INTERACTIONS （ 影响因子：5.168； 五年影响因子：4.924 ）

ISSN： 0009-2797

年卷期： 2017 年 272 卷

页码：

收录情况： SCI

摘要： Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7 alpha-hydroxylase 1 (CYP7A1) and sterol 12 alpha-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting poly peptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. (C) 2017 Elsevier B.V. All rights reserved.

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