As the experimental findings discussed here indicate that elevated pyruvate carboxylation may be a significant part of the pathogenesis of glutamatergic hyperactivity and comorbid obesity in bipolar disorder, designing inhibitors of pyruvate carboxylase to pharmacologically modulate pyruvate carboxylase-mediated anaplerosis may be a useful new treatment strategy for bipolar disorder and comorbid obesity. Here, PC is linked to obesity due to melanocortin 4 receptor deficiency.