High soluble endoglin levels regulate cholesterol homeostasis and bile acids turnover in the liver of transgenic mice
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
31299237
DOI
10.1016/j.lfs.2019.116643
PII: S0024-3205(19)30569-7
Knihovny.cz E-zdroje
- Klíčová slova
- Bile acids, Bile production, Cholesterol, Endoglin, Liver,
- MeSH
- cholesterol krev metabolismus MeSH
- endoglin krev fyziologie MeSH
- feces MeSH
- homeostáza * MeSH
- játra metabolismus MeSH
- myši transgenní MeSH
- myši MeSH
- oxidační stres MeSH
- přenašeče organických aniontů závislé na sodíku metabolismus MeSH
- protein SREBP2 metabolismus MeSH
- receptory LDL metabolismus MeSH
- symportéry metabolismus MeSH
- upregulace MeSH
- zánět krev MeSH
- žlučové kyseliny a soli krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- endoglin MeSH
- Eng protein, mouse MeSH Prohlížeč
- přenašeče organických aniontů závislé na sodíku MeSH
- protein SREBP2 MeSH
- receptory LDL MeSH
- sodium-bile acid cotransporter MeSH Prohlížeč
- Srebf2 protein, mouse MeSH Prohlížeč
- symportéry MeSH
- žlučové kyseliny a soli MeSH
AIMS: Increased plasma soluble endoglin concentrations (sEng) are frequently detected in metabolic disorders accompanied with hypercholesterolemia in serum, but effect of sEng on the cholesterol biochemistry is unknown. Cholesterol and bile acids (BA) are important products of liver metabolism with numerous functions within the organism. Turnover of these substances requires precise regulation due to potential toxicities during their cumulation. In this study, we hypothesized that high sEng levels affect cholesterol homeostasis and BA turnover in mice liver. MAIN METHODS: Nine-month-old transgenic male mice overexpressing human sEng and wild-type mice underwent plasma, bile, stool, and organ samples analysis by analytical, qRT-PCT and Western blot methods. KEY FINDINGS: sEng mice demonstrated decreased plasma total and LDL cholesterol concentrations due to upregulation of hepatic Sr-b1 and Ldlr receptors, increased liver cholesterol content, and increased Abcg8-mediated cholesterol efflux into bile. sEng also increased conversion of cholesterol into bile acids (BA) via upregulation of Cyp7a1 and increased Mdr1 expression. Plasma concentrations of BA were increased in sEng mice due to their enhanced reabsorption via ileum. Increased hepatic disposition of BA led to their increased biliary excretion coupled with choleretic activity. SIGNIFICANCE: For the first time, we have shown that high sEng plasma levels affect cholesterol and BA homeostasis on the basis of complex liver and intestinal effects. The significance of these findings for pathophysiology of diseases associated with increased sEng concentrations remains to be elucidated in prospective studies.
Centrum for Research and Development University Hospital Hradec Kralove Czech Republic
Department of Biochemistry Faculty of Medicine in Hradec Kralove Charles University Czech Republic
Department of Pharmacology Faculty of Medicine in Hradec Kralove Charles University Czech Republic
Citace poskytuje Crossref.org
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