The effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on fatty acid oxidation in hepatocytes isolated from neonatal piglets
Abstract 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 37and#176;C had no significant effect on total [1-14C]-palmitate (0.5 mM) oxidation (14CO2 and 14C-Acid soluble products (ASP)). Consistent with the fatty acid oxidation, carnitine palmitoyltransferase I activity and inhibition of its activity by malonyl-CoA (10 and#956;M) assayed in cell homogenate also remained constant. However, addition of AICAR to the hepatocytes decreased 14CO2 production by 18% compared to control (p andlt; 0.06). The reduction of labeled carboxylic carbon accumulated in CO2 caused a significant difference in distribution of oxidative products between 14CO2 and 14C-ASP (p andlt; 0.03) compared with the control. It was also noticed that acetyl-CoA carboxylase (ACC) was increased by AICAR (p andlt; 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 14C-ASP. Addition of insulin to hepatocyte incubations with AICAR did not change the oxidative product distribution between CO2 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.
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Journal of Animal Science and Biotechnology. 2012 Oct 17;3(1):30