Figure 1. SBI-0206965 dose dependently attenuates 991-induced phosphorylation of ACC and inhibition of lipogenesis in mouse primary hepatocytes.

(A,B) Mouse primary hepatocytes were pre-incubated for 30 min with vehicle (0.1% DMSO) or the indicated concentrations of SBI-0206965 followed by an additional incubation for 1 h with 991 (10 μM) or vehicle. Cell lysates were subjected to immunoblot analysis using the indicated antibodies. Tubulin was used as a loading control. Representative images (A) and quantification of the indicated blots (B) from three independent experiments are shown (n = 6 per treatment). (C) Mouse hepatocytes were treated with the indicated concentrations of SBI-0206965 in the absence (vehicle) or presence of 991 (10 μM) and labelled with [¹⁴C]-acetate for 3 h. Rates of fatty acid synthesis were estimated from incorporation [¹⁴C]-acetate into saponifiable lipids. (D) Results from (B) and (C) (except vehicle and SBI-0206965 alone data) are plotted to visualise the inverse relationship between ACC phosphorylation and lipogenesis in response to increasing doses of SBI-0206965 in combination with 991 (10 μM). Results are expressed as percentage relative to the vehicle and represent the mean ± SEM for three independent experiments (n = 6–12 per treatment). *P < 0.05 (vehicle vs. indicated compound(s) treated). N.S.; not significant.