Hepatic and skeletal muscle glycogen metabolism in rats with short-term cholestasis

Background/Aims: To study the effect of short-term cholestasis on glycogen metabolism. Methods: Rats were bile duct ligated (BDL) for 4 or 8 days and compared to sham-operated control rats pair-fed to BDL (pair-fed CON) or fed ad libitum (ad libitum-fed CON). Results: Four days after surgery, the hepatic glycogen content was 21.6±7.6 mg/g in BDL, 21.2±8.5 mg/g in pair-fed CON and 72.9±7.7 mg/g in ad libitum-fed CON, respectively. Eight days after surgery, the hepatic glycogen content was reduced in BDL as compared to pair-fed (31.2±8.9 vs. 59.1±5.4 mg/g) or ad libitum-fed CON (58.3±4.7 mg/g). Similar findings were obtained with the glycogen content expressed per ml hepatocytes or per liver. Histological analysis of BDL livers showed that most hepatocytes were affected. As compared to CON, activities and mRNA levels of glycogen synthase and phosphorylase were reduced in BDL, whereas plasma glucagon and endotoxin levels were increased at both time points. In contrast to liver, skeletal muscle glycogen metabolism remained unaffected. Conclusions: While reduced intake of food explains the decrease in the hepatic glycogen stores in BDL and pair-fed CON 4 days after surgery, reduced glycogen synthesis, possibly related to endotoxinemia, is the most probable cause of the decrease in the hepatic glycogen content in BDL 8 days after surgery.