Lipogenic effects of psychotropic drugs: focus on the SREBP system

Antipsychotics, antidepressants and mood stabilizers are psychotropic drugs widely used in the treatment of psychiatric disorders, such as schizophrenia, bipolar disorder and major depressive disorder. Such drugs have been used since the early 1950s, and it is now well established that they target neurotransmitter receptors and/or transporters located on central nervous system (CNS) neurons. However, their mechanism of action is still not fully understood, and there is large inter-individual variation in therapeutic response. Psychotropic drugs are also associated with numerous adverse effects, of which weight gain and metabolic disturbances have gained increased focus during the last decade. Based on studies in cultured cells, we have demonstrated that several psychotropic drugs upregulate the expression of genes involved in cellular fatty acid and cholesterol biosynthesis, controlled by the SREBP transcription factors. Lipogenic effects were also observed in vivo, in rat liver and in lymphocytes from drug-treated patients. These results provide new insight into the molecular mechanisms of psychotropic drug action and could be relevant both for their therapeutic action and metabolic adverse effects.