Figure 1

The effect of clozapine on lipogenic gene expression in GaMg cells. Gene expression was determined in GaMg cells after exposure of various concentrations of clozapine for 24 hours. The level of expression was measured by quantitative RT-PCR, relative to the expression of the ribosomal gene P0. The p-values were obtained by a Dunnett post-hoc test following a one-way ANOVA. Error bars display ± SEM, and the data are representative of three independent parallel experiments. A) Relative expression levels of genes involved in cholesterol biosynthesis (filled symbols), cholesterol transport and fatty acid biosynthesis (open symbols). The expression of all genes was significantly increased (fold change at 50 μM clozapine, p-value): stearoyl-CoA desaturase (delta-9-desaturase; SCD1) (7.4, p = 0.000008), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) (5.6, p = 0.000009), fatty acid synthase (FASN) (5.4, p = 0.000008), 7-dehydrocholesterol reductase (DHCR7) (4.3, p = 0.000008), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (3.1, p = 0.00001), sterol-C5-desaturase like (SC5DL) (3.1, p = 0.00001), acetyl-CoA acetyltransferase 2 (also termed acetoacetyl-CoA thiolase; ACAT2) (3.0, p = 0.00009), low density lipoprotein receptor (LDLR) (2.8, p = 0.00001) and farnesyl diphosphate synthase (FDPS) (2.8, p = 0.000009). B) Relative expression levels of SREBP1a (open symbols) and SREBP2 (filled symbols). Both SREBP1a (2.2-fold, p = 0.02) and SREBP2 (2.5-fold, p = 0.0002) were increased by clozapine in a dose-dependent manner.