PMID- 28549616 OWN - NLM STAT- MEDLINE DCOM- 20170620 LR - 20181202 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 272 DP - 2017 Jun 25 TI - Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice. PG - 153-159 LID - S0009-2797(17)30293-4 [pii] LID - 10.1016/j.cbi.2017.05.018 [doi] AB - 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 7alpha-hydroxylase 1 (CYP7A1) and sterol 12alpha-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 polypeptide (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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Zhu, Ru-Gang AU - Zhu RG AD - Department of Food Science, College of Light Industry, Liaoning University, Liaoning Engineering Research Center for Food Bioprocessing, Shenyang Key Laboratory of Food Bioprocessing and Quality Control, Shenyang 110036, China. Electronic address: zhurugang@lnu.edu.cn. FAU - Sun, Yan-Di AU - Sun YD AD - Department of Food Science, College of Light Industry, Liaoning University, Liaoning Engineering Research Center for Food Bioprocessing, Shenyang Key Laboratory of Food Bioprocessing and Quality Control, Shenyang 110036, China. FAU - Hou, Yu-Ting AU - Hou YT AD - Department of Food Science, College of Light Industry, Liaoning University, Liaoning Engineering Research Center for Food Bioprocessing, Shenyang Key Laboratory of Food Bioprocessing and Quality Control, Shenyang 110036, China. FAU - Fan, Jun-Gang AU - Fan JG AD - Forestry Biotechnology and Analysis Test Center, Liaoning Academy of Forestry Sciences, Shenyang 110032, China. FAU - Chen, Gang AU - Chen G AD - Forestry Biotechnology and Analysis Test Center, Liaoning Academy of Forestry Sciences, Shenyang 110032, China. FAU - Li, Tuo-Ping AU - Li TP AD - College of Food Science, Shenyang Agriculture University, Shenyang 110032, China. Electronic address: Ltp0401@126.com. LA - eng PT - Journal Article DEP - 20170523 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (ABCA1 protein, mouse) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (Apolipoprotein A-I) RN - 0 (Bile Acids and Salts) RN - 0 (Cholesterol, HDL) RN - 0 (Oligosaccharides) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class B) RN - 89NA02M4RX (Pectins) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase) RN - EC 1.14.14.23 (Cyp7a1 protein, mouse) RN - EC 1.14.18.8 (Steroid 12-alpha-Hydroxylase) SB - IM MH - ATP Binding Cassette Transporter 1/genetics/metabolism MH - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/metabolism MH - Animals MH - Apolipoprotein A-I/blood MH - Bile Acids and Salts/*metabolism MH - Cholesterol/*blood MH - Cholesterol 7-alpha-Hydroxylase/genetics/metabolism MH - Cholesterol, HDL/blood MH - Diet, High-Fat MH - Gene Expression/*drug effects MH - Intestine, Small/drug effects/metabolism MH - Liver/drug effects/metabolism MH - Male MH - Mice MH - Oligosaccharides/*pharmacology MH - Pectins/chemistry/*pharmacology MH - Scavenger Receptors, Class B/genetics/metabolism MH - Steroid 12-alpha-Hydroxylase/genetics/metabolism OTO - NOTNLM OT - Bile acids synthesis OT - Cholesterol accumulation OT - Excretion OT - Haw pectin penta-oligogalacturonide OT - Transport EDAT- 2017/05/28 06:00 MHDA- 2017/06/21 06:00 CRDT- 2017/05/28 06:00 PHST- 2017/03/15 00:00 [received] PHST- 2017/05/15 00:00 [revised] PHST- 2017/05/22 00:00 [accepted] PHST- 2017/05/28 06:00 [pubmed] PHST- 2017/06/21 06:00 [medline] PHST- 2017/05/28 06:00 [entrez] AID - S0009-2797(17)30293-4 [pii] AID - 10.1016/j.cbi.2017.05.018 [doi] PST - ppublish SO - Chem Biol Interact. 2017 Jun 25;272:153-159. doi: 10.1016/j.cbi.2017.05.018. Epub 2017 May 23.