title: Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.
abstract: Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and cholesterol efflux.
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China; Department of Scientific Research, Logistics University of Chinese People's Armed Police Forces, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China; School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Zongkai
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Pu
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin, China. Electronic address: guocjtj@126.com.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Guo
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006903:Hydroxymethylglutaryl CoA Reductases; D000071518:Liver X Receptors; D011794:Quercetin; D012333:RNA, Messenger; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; C577834:Abca1 protein, rat; C559724:Abcg1 protein, rat; C000605215:Nr1h3 protein, rat; C532838:CYP7A1 protein, rat
keywords: Bile acids; Cholesterol; Lipid metabolism; Quercetin; Rats