Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction.
Details
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_651BA8C7C141
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction.
Journal
Journal of hepatology
ISSN
0168-8278 (Print)
ISSN-L
0168-8278
Publication state
Published
Issued date
11/2002
Peer-reviewed
Oui
Volume
37
Number
5
Pages
564-571
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
Anastomosis, Roux-en-Y, Animals, Bile Ducts/surgery, Cholestasis, Extrahepatic/metabolism, Cholestasis, Extrahepatic/surgery, Electron Transport/physiology, Fatty Acids/metabolism, Hydroxymethylglutaryl-CoA Synthase/metabolism, Ketones/metabolism, Ligation, Liver/enzymology, Male, Mitochondria/metabolism, Oxidation-Reduction, Rats, Rats, Sprague-Dawley
Pubmed
Open Access
Yes
Create date
11/12/2018 15:26
Last modification date
03/05/2023 11:34
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