[Frontiers in Bioscience 16, 49-60, January 1, 2011]

Lipogenic effects of psychotropic drugs: focus on the SREBP system

Johan Ferno1,2, Silje Skrede1,2, Audun Osland Vik-Mo1,2, Goran Jassim1,2, Stephanie Le Hellard1,2, Vidar Martin Steen1,2

1Department of Clinical Medicine, Dr. Einar Martens' Research Group for Biological Psychiatry and Bergen Mental Health Research Center, University of Bergen, Bergen, Norway, 2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Antipsychotic drugs influence the expression of lipogenic genes in cultured cells
4. Lipid biosynthesis and the SREBP transcription system
5. Antipsychotic drugs stimulate proteolytic SREBP activation in vitro
6. Lipogenic effects in vitro as a common property of antipsychotic drugs
7. SREBP activation: a shared feature among different classes of psychotropic drugs
8. Lipogenic effects of psychotropic drugs in vitro: a novel mechanism of action?
9. Antipsychotic-induced effects on SREBP-controlled gene expression in vivo
10. Genetic variation in SREBP-related genes is relevant for metabolic adverse effects and disease susceptibility in patients with schizophrenia
11. Perspectives
12. Acknowledgements
13. References

1. ABSTRACT

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.