Fig. 6.
Proposed mechanism on ethanol effects on AMPK phosphorylation. The inhibitory effect of ethanol on AMPK phosphorylation was attenuated by the presence of an acid sphingomyelinase (SMase) inhibitor (imipramine) or ceramide synthase inhibitor (fumonisin B1) in hepatoma cells. Ethanol also increased the mRNA levels of acid SMase in ethanol-fed mice. We propose that the inhibitory effects of ethanol on AMPK phosphorylation are secondary to increased intracellular ceramide concentrations (through increased acid SMase activity), leading to increase in PP2A activity, thus inhibiting AMPK phosphorylation. SPT, serine palmitoyl transferase.