Dose-dependent inhibition of de novo lipogenesis by (A) Met and (B) salicylate in mouse hepatocytes. (C) Ser79/212 P-ACC as a downstream target and marker of AMPK activation in primary mouse hepatocytes treated with no drug (Con), Met, salicylate (Sal) or Met + salicylate. (D) Inverse suppression of lipogenesis in mouse hepatocytes using the drug concentrations in (C). (E) CI compared with fractional effect inhibition (Fa) of lipogenesis in mouse hepatocytes treated with Met + salicylate (concentration ratio of 1:10 Met–salicylate) where CI > 1 indicates an antagonistic, CI = 1 additive or CI < 1 synergistic inhibition. Results represent at least two independent experiments performed in triplicate. (F) Fatty acid oxidation in mouse hepatocytes treated with no drug, low dose Met (0.1 mM), salicylate (0.5 mM) or both. Results from two independent experiments performed in triplicate. (G) Activation of AMPK by salicylate + AMP in vitro using purified, dephosphorylated AMPK α1β1γ1. Results were generated from four independent experiments. All densitometry is a ratio of phosphorylated to total protein. Data are means ± S.E.M. except panel (E), which are −means only. *P < 0.05 compared with Con, ‡ P < 0.05 compared with both respective Met-only and Sal-only doses.