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Impaired cholesterol metabolism in the mouse model of cystic fibrosis. A preliminary study.

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  • معلومة اضافية
    • المصدر:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: San Francisco, CA : Public Library of Science
    • الموضوع:
      Lipid Metabolism* ; Mutation*; Cholesterol/*metabolism ; Cystic Fibrosis/*pathology ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Liver/*metabolism ; Steroid Hydroxylases/*metabolism; Animals ; Cystic Fibrosis/genetics ; Cystic Fibrosis/metabolism ; Female ; Homozygote ; Male ; Metabolic Clearance Rate ; Mice
    • نبذة مختصرة :
      This study aims to investigate cholesterol metabolism in a mouse model with cystic fibrosis (CF) by the comparison of affected homozygous versus wild type (WT) mice. In particular, we evaluated the effects of a diet enriched with cholesterol in both mice groups in comparison with the normal diet. To this purpose, beyond serum and liver cholesterol, we analyzed serum phytosterols as indirect markers of intestinal absorption of cholesterol, liver lathosterol as indirect marker of de novo cholesterol synthesis, liver cholestanol (a catabolite of bile salts synthesis) and the liver mRNA levels of LDL receptor (LDLR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR), acyl CoA:cholesterol acyl transferase 2 (ACAT2), cytochrome P450 7A1 (CYP7A1) and tumor necrosis factor alpha (TNFα). CF mice showed lower intestinal absorption and higher liver synthesis of cholesterol than WT mice. In WT mice, the cholesterol supplementation inhibits the synthesis of liver cholesterol and enhances its catabolism, while in CF mice we did not observe a reduction of LDLR and HMG-CoAR expression (probably due to an altered feed-back), causing an increase of intracellular cholesterol. In addition, we observed a further increase (5-fold) in TNFα mRNA levels. This preliminary study suggests that in CF mice there is a vicious circle in which the altered synthesis/secretion of bile salts may reduce the digestion/absorption of cholesterol. As a result, the liver increases the biosynthesis of cholesterol that accumulates in the cells, triggering inflammation and further compromising the metabolism of bile salts.
      Competing Interests: The authors have declared that no competing interests exist.
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    • الرقم المعرف:
      0 (Cftr protein, mouse)
      126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
      97C5T2UQ7J (Cholesterol)
      EC 1.14.- (Steroid Hydroxylases)
    • الموضوع:
      Date Created: 20210107 Date Completed: 20210906 Latest Revision: 20210906
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC7790534
    • الرقم المعرف:
      10.1371/journal.pone.0245302
    • الرقم المعرف:
      33412572