The effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on fatty acid oxidation in hepatocytes isolated from neonatal piglets

In the present study, the effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on long-chain fatty acid oxidation by hepatocytes isolated from suckled neonatal pig liver (a low ketogenic and lipogenic tissue) was tested. Incubation of hepatocytes with AICAR (0.5 mM) in the presence of 1 mM of carnitine and 10 mM of glucose for 1 hour at 37°C had no significant effect on total [1-(14)C]-palmitate (0.5 mM) oxidation ((14)CO(2) and (14)C-Acid soluble products (ASP)). Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyl-CoA (10 μM) assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased (14)CO(2) production by 18% compared to control (p < 0.06). The reduction of labeled carboxylic carbon accumulated in CO(2) caused a significant difference in distribution of oxidative products between (14)CO(2) and (14)C-ASP (p < 0.03) compared with the control. It was also noticed that acetyl-CoA carboxylase (ACC) was increased by AICAR (p < 0.03), indicating that ACC might drive acetyl-CoA toward fatty acid synthesis pathway and induce an increase in distribution of fatty acid carbon to (14)C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO(2) and ASP, but further promoted ACC activity. The increased ACC activity was 70% higher than in the control group when citrate was absent in the reaction medium and was 30% higher when citrate was present in the medium. Our results suggest that AICAR may affect the distribution of metabolic products from fatty acid oxidation by changing ACC activity in hepatocyte isolated from suckled neonatal piglets; however, the basis for the increase in ACC activity elicited by AICAR is not apparent.