The results suggest that, besides its well-known effects in targeting “HMG-CoA reductase”, simvastatin co-treatment may ameliorate olanzapine-induced dyslipidemia through inhibiting SREBP-controlled HMG-CoA reductase activation, and modulating the transcriptional responses of thermogenic genes, at least in part, to increase energy expenditure via upregulation of UCP1. This evidence concerns the gene HMGCR and metabolic syndrome.