Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

Anitta K Sárvári; Zoltán Veréb; Iván P Uray; László Fésüs; Zoltán Balajthy

doi:10.1016/j.bbrc.2014.07.005

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

Biochem Biophys Res Commun. 2014 Aug 8;450(4):1383-9. doi: 10.1016/j.bbrc.2014.07.005. Epub 2014 Jul 11.

Authors

Anitta K Sárvári¹, Zoltán Veréb², Iván P Uray³, László Fésüs⁴, Zoltán Balajthy⁵

Affiliations

¹ Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. Electronic address: anittasarvari@med.unideb.hu.
² Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. Electronic address: jzvereb@gmail.com.
³ Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ipuray@mdanderson.org.
⁴ Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences, Hungary. Electronic address: fesus@med.unideb.hu.
⁵ Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. Electronic address: balajthy@med.unideb.hu.

PMID: 25019983
DOI: 10.1016/j.bbrc.2014.07.005

Abstract

Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state.

Keywords: Atypical antipsychotics; Clozapine; Inflammation; Olanzapine; Psychiatric disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / cytology
Adipocytes / drug effects*
Adipocytes / metabolism
Adipogenesis / genetics*
Antipsychotic Agents / pharmacology*
Cell Differentiation
Gene Expression Regulation / drug effects*
Humans
In Vitro Techniques
Inflammation Mediators / metabolism*
Polymerase Chain Reaction

Substances

Antipsychotic Agents
Inflammation Mediators