Titre
Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction.
Type
article
Institution
Externe
Périodique
Auteur(s)
Lang, C.
Auteure/Auteur
Berardi, S.
Auteure/Auteur
Schäfer, M.
Auteure/Auteur
Serra, D.
Auteure/Auteur
Hegardt, F.G.
Auteure/Auteur
Krähenbühl, L.
Auteure/Auteur
Krähenbühl, S.
Auteure/Auteur
Liens vers les personnes
ISSN
0168-8278
Statut éditorial
Publié
Date de publication
2002-11
Volume
37
Numéro
5
Première page
564
Dernière page/numéro d’article
571
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Rats with long-term cholestasis have reduced ketosis of unknown origin.
Fatty acid metabolism was studied in starved rats with biliary obstruction for 4 weeks (bile duct ligated rats = BDL rats), and 3, 7, 14, 28 and 84 days after reversal of biliary obstruction by Roux-en-Y anastomosis (RY rats), and in sham-operated control rats.
BDL rats had reduced beta-hydroxybutyrate concentrations in plasma (0.25 +/- 0.10 vs. 0.75 +/- 0.20 mmol/l) and liver (2.57 +/- 0.20 vs. 4.63 +/- 0.61 micromol/g) which increased after restoring bile flow. Hepatic expression and activity of carnitine palmitoyltransferase I (CPT I) or CPT II were unaffected or decreased in BDL rats, respectively, and increased after restoring bile flow. Oxidative metabolism of different substrates by isolated liver mitochondria and activation of palmitate were reduced in BDL rats and recovered 7-14 days after restoring bile flow. Ketogenesis was decreased in mitochondria from BDL rats and recovered 3 months after restoring bile flow. Both mRNA and protein expression of hydroxymethylglutaryl-coenzyme A synthase (HMG-CoA synthase), the rate-limiting enzyme of ketogenesis, was reduced in livers of BDL rats and increased after reversing biliary obstruction.
In BDL rats, impairment of hepatic fatty acid metabolism is multifactorial. After reversing biliary obstruction, reduced activity of HMG-CoA synthase is the major factor.
Fatty acid metabolism was studied in starved rats with biliary obstruction for 4 weeks (bile duct ligated rats = BDL rats), and 3, 7, 14, 28 and 84 days after reversal of biliary obstruction by Roux-en-Y anastomosis (RY rats), and in sham-operated control rats.
BDL rats had reduced beta-hydroxybutyrate concentrations in plasma (0.25 +/- 0.10 vs. 0.75 +/- 0.20 mmol/l) and liver (2.57 +/- 0.20 vs. 4.63 +/- 0.61 micromol/g) which increased after restoring bile flow. Hepatic expression and activity of carnitine palmitoyltransferase I (CPT I) or CPT II were unaffected or decreased in BDL rats, respectively, and increased after restoring bile flow. Oxidative metabolism of different substrates by isolated liver mitochondria and activation of palmitate were reduced in BDL rats and recovered 7-14 days after restoring bile flow. Ketogenesis was decreased in mitochondria from BDL rats and recovered 3 months after restoring bile flow. Both mRNA and protein expression of hydroxymethylglutaryl-coenzyme A synthase (HMG-CoA synthase), the rate-limiting enzyme of ketogenesis, was reduced in livers of BDL rats and increased after reversing biliary obstruction.
In BDL rats, impairment of hepatic fatty acid metabolism is multifactorial. After reversing biliary obstruction, reduced activity of HMG-CoA synthase is the major factor.
PID Serval
serval:BIB_651BA8C7C141
PMID
Open Access
Oui
Date de création
2018-12-11T13:26:40.955Z
Date de création dans IRIS
2025-05-20T18:55:21Z
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