AMPK Activator AICAR Inhibits Hepatic Gluconeogenesis and Fatty Acid Oxidation

Kim, Jin Yob; Koh, Eun Hee; Lee, Woo Je; Han, Seong Min; Youn, Ji Young; Park, Hye Sun; Kim, Hyun Sik; Kim, Min Seon; Park, Joong Yeol; Lee, Ki Up

Abstract

BACKGROUND: Recent studies have demonstrated that adiponectin and metformin activate AMPK in the liver, and adiponectin and metformin stimulate fatty acid oxidation while inhibiting glucose production in liver. These results are in contrast to previous studies that have demonstrated that increased fatty acid oxidation in the liver is associated with increased gluconeogenesis. The present study was undertaken to reinvestigate the effects of AMPK activation by AICAR on hepatic fatty acid oxidation and gluconeogenesis.
METHODS
HePG2 cells were treated with various concentrations of AICAR, and then the fatty acid oxidation and gluconeogenesis of the cells were determined. To investigate the in vivo effect of AICAR, Sprague-Dawely rats were infused with AICAR (bolus, 40 mg/g; constant, 7.5 mg/g/min-1) for 90min.
RESULTS
Incubation of the HePG2 cells with higher concentrations (=1 mM) of AICAR increased fatty acid oxidation and gluconeogenesis. On the other hand, incubation of HePG2 cells with lower concentrations (0.05 and 0.1 mM) of AICAR decreased fatty acid oxidation and gluconeogenesis. Consistent with this in vitro data, the intravenous administration of AICAR to rats lowered their plasma glucose concentration and inhibited hepatic gluconeogenesis. Fatty acid oxidation in the liver tissue was significantly decreased by the administration of AICAR.
CONCLUSION
The present study has demonstrated that AICAR decreased gluconeo-genesis in the liver. In contrast to previous studies, AICAR profoundly decreased hepatic fatty acid oxidation in rats and also in cultured hepatocytes