Abstract
Background/Aims: Rats with long-term bile duct ligation (BDL rats) have impaired hepatic fatty acid
metabolism and alterations in carnitine homeostasis. Analysis of the carnitine tissue
and body fluid pools was used as a tool to study hepatic fatty acid metabolism in
BDL rats and after reversal of bile duct ligation by Roux-en-Y anastomosis for 5 (RY5)
or 14 days (RY14).
Methods: Control rats were pair-fed to treated rats, and all rats were studied after starvation
for 24 h. Carnitine was analyzed by a radioenzymatic method and by high performance
liquid chromatography.
Results: Both BDL and RY rats had decreased plasma β-hydroxybutyrate concentrations, whereas
free fatty acid plasma concentrations were not different from control rats. Free carnitine
plasma concentrations were not different between BDL or RY and control rats, whereas
acetylcarnitine concentrations were decreased in BDL and RY rats, and showed a positive
correlation with the plasma β-hydroxybutyrate concentrations. In comparison to control
rats, the total hepatic carnitine content was increased in BDL and RY rats, both when
expressed per g tissue and per total liver. This rise in the hepatic carnitine content
was due to increases in both free and acylcarnitines, including acetylcarnitine. In
comparison to control rats, the hepatic concentration of ß-hydroxybutyrate was decreased
in BDL and RY rats, findings compatible with impaired formation of ketone bodies from
acetyl-CoA. Urinary excretion of total carnitine was not different between treated
and control rats.
Conclusions: Hepatic metabolism of fatty acids is impaired in BDL rats and does not recover during
the 14 days after Roux-en-Y anastomosis. The increased hepatic carnitine content in
BDL and RY rats can best be explained by decreased export of carnitine from the hepatocytes.
The alterations in the hepatic carnitine pool and impaired hepatic fatty acid metabolism
in BDL and RY rats are compatible with impaired ketogenesis.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The evolution of changes in quantitative liver function tests in a rat model of biliary cirrhosis: correlation with morphometric measurement of hepatocyte mass.Hepatology. 1987; 7: 457-463
- Reversibility of secondary biliary fibrosis by biliodigestive anastomosis in the rat.Gastroenterology. 1992; 103: 579-589
- Rapid normalization of the hepatic glycogen metabolism in rats with biliary cirrhosis after biliodigestive anastomosis.J Hepatol. 1997; 26: 75
- Progressive decrease in tissue glycogen content in rats with long-term cholestasis.Hepatology. 1996; 24: 902-907
- Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis.Hepatology. 1991; 14: 927-934
- Mechanisms of impaired hepatic fatty acid metabolism in rats with long-term bile duct ligation.Hepatology. 1994; 19: 1272-1281
- Reversibility of hepatic mitochondrial damage in rats with long-term cholestasis.J Hepatol. 1998; 28: 1000-1007
- Carnitine metabolism in the fasting rat.J Biol Chem. 1978; 253: 2688-2693
- Relationship between acid-soluble carnitine and coenzyme A pools in vivo.Biochem J. 1980; 190: 495-504
- Carnitine and derivatives in rat tissues.Biochem J. 1967; 105: 953-963
- An enzymatic fluorometric micromethod for the determination of acetoacetate, β-hydroxybutyrate, pyruvate and lactate.Clin Chim Acta. 1971; 33: 293-300
- A method for the determination of carnitine in the picomolar range.Clin Chim Acta. 1972; 37: 235-243
- Quantification of free carnitine, individual short- and medium-chain acylcarnitines, and total carnitine in plasma by high-performance liquid chromatography.Anal Biochem. 1993; 212: 510-518
- A specific renal defect in carnitine biosynthesis in rats with secondary biliary cirrhosis.J Hepatol. 1992; 16: S71
- Carnitine: metabolism and functions.Physiol Rev. 1983; 63: 1421-1466
- Carnitine and trimethylaminobutyrate synthesis in rat tissues.Biochem J. 1974; 142: 699-701
- Hydroxylation δ-buytrobetaine to carnitine in rat liver.Biochemistry. 1967; 6: 1271-1282
- Transport and metabolism of carnitine precursors in various organs of the rat.Biochem Biophys Acta. 1980; 631: 192-202
- Release of carnitine from the perfused rat liver.Biochim Biophys Acta. 1985; 835: 83-91
- Carnitine and carnitine esters in rat bile and human duodenal fluid.Can J Physiol Pharmacol. 1986; 65: 1816-1820
- The mitochondrial carnitine palmitoyl-transferase system. From concept to molecular analysis.Eur J Biochem. 1997; 244: 1-14
- Regulation of fatty acid oxidation in mammalian liver.Biochim Biophys Acta. 1993; 1167: 227-241
- Glucagon activates mitochondrial 3-hydroxy-3methylglutaryl-CoA synthase in vivo by decreasing the extent of succinylation of the enzyme.Eur J Biochem. 1990; 187: 169-174
- Vasopressine gene expression in rats with experimental cirrhosis.Hepatology. 1993; 17: 143-147
- Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis.Hepatology. 1991; 14: 103-111
- Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.Clin Endocrinol Metab. 1993; 77: 1263-1268
- Surplus acylcarnitines in the plasma of starved rats derive from the liver.J Biol Chem. 1990; 265: 22313-22316
Article info
Publication history
Accepted:
September 15,
1998
Received in revised form:
August 24,
1998
Received:
March 14,
1998
Identification
Copyright
© 1999 Published by Elsevier Inc.
