Rapid normalization of hepatic glycogen metabolism in rats with long-term bile duct ligation after biliodigestive anastomosis.

BACKGROUND/AIMS: Rats with chronic bile duct ligation have reduced hepatic glycogen stores and decreased activities of enzyme involved in glycogen metabolism. In the current studies, the reversibility of these changes following reversal of biliary obstruction by Roux-en-Y anastomosis (RY) was investigated.

METHODS

Rats were studied after bile duct ligation for 4 weeks (BDL rats), or 5 or 14 days after relief of biliary obstruction by RY. Control rats were pair-fed to treated rats, and all rats were studied in the fed state.

RESULTS

The liver glycogen content was decreased in BDL rats (198+/-167 vs. 753+/-315 mg/liver in BDL vs. control rats) and normalized within 5 days after RY. The total activities of glycogen synthase and phosphorylase were both reduced by 51% in BDL as compared to control rats. Five days after RY, the activity of glycogen synthase had increased significantly in comparison to BDL rats, whereas glycogen phosphorylase had remained unchanged. Fourteen days after RY, both enzyme activities had completely normalized. Northern blots revealed reduced hepatic mRNA levels in BDL rats, for glycogen synthase and phosphorylase. While the mRNA level for glycogen synthase normalized within 5 days after RY, the level for glycogen phosphorylase increased but did not normalize completely within 14 days after RY.

CONCLUSIONS

Hepatic glycogen stores are decreased in BDL rats but recover rapidly after relief of biliary obstruction. Reduced activity and mRNA levels of glycogen synthase suggest that impaired glycogen synthesis is the principal mechanism for decreased hepatic glycogen stores in BDL rats.