Glucose homeostasis and fatty acid metabolism are abnormal in patients with cirrhosis. To assess the metabolic response to starvation in an animal model of cirrhosis, glycogen and fuel metabolism were characterized in rats with CC1,-induced cirrhosis studied 2 wk after 10 weekly doses of CCl,. Plasma concentrations of glucose and fbhydroxybutyrate were not different between fed CC1,-treated and control rats, but plasma nonesterified fatty acid concentrations were higher in cirrhotic animals (0.25 f 0.01 vs. 0.39 f 0.04 mmolb; p < 0.05). After 12 hr of starvation, the plasma nonesterified fatty acid concentration had reached 0.58 f 0.04 mmoln in CC1,-treated rats, compared with 0.38 2 0.04 mmolb in control rats (p < 0.05). The redistribution of the hepatic carnitine pool toward acylcarnitines, which is characteristic of starvation, was complete after fasting for 12 hr in the CC1,-treated rats, compared with the 24 hr required in control rats. In fed cirrhotic rats, liver glycogen content per gram liver was decreased by 644 compared with control rats (30.0 -t 5.1 vs. 10.8 2 1.1 mg/gm liver wet wt; p < 0.05).
After 12-hr fasting, hepatic glycogen content had fallen to 14.3 2 3.9 and 4.8 f 0.4 mg/gm liver wet w t (p < 0.05) in control and cirrhotic animals, respectively. To further characterize the status of glycogen metabolism in cirrhotic livers, activities of glycogen synthase and glycogen phosphorylase were determined. Hepatic active and total glycogen phosphorylase activities normalized to hepatocellular content were unaffected by CCl, treatment, whereas total glycogen synthase activity was increased by 45%. In conclusion, hepatic glycogen content in fed animals with CC1,-induced cirrhosis is decreased, and cirrhotic animals have accelerated transition from the fed to the fasted state, as evidenced by hepatic glycogen depletion, increased plasma nonesterified fatty acid concentrations and redistribution of the hepatic carnitine pool. Rats with CC1,-induced liver cirrhosis provide a useful animal