Olanzapine promotes the accumulation of lipid droplets and the expression of multiple perilipins in human adipocytes.

Abstract

Second generation antipsychotics are useful for the treatment of schizophrenia, but concerns have been raised about the side effects of diabetes mellitus and obesity. Olanzapine, especially, is associated with more weight gain than the others. It has been reported that olanzapine promotes adipocyte-differentiation in rodents both in vivo and in vitro. In this study the effects of antipsychotics on human adipocytes were investigated by using human mesenchymal stem cells (hMSCs). When hMSCs were differentiated and treated with various antipsychotics, olanzapine and clozapine increased intracellular lipids. Olanzapine induced lipid accumulation in a dose-dependent manner. Proteomic analysis revealed that PLIN4 and several enzymes for lipid metabolism were increased in the hMSCs after olanzapine treatment. During adipocyte differentiation, olanzapine increased the protein expression of PLIN1, PLIN2 and PLIN4. These proteins are known to be associated with the initial stage of lipid droplet formation. Immunocytochemistry showed that olanzapine increased and enlarged the lipid droplets coated with PLIN1 and PLIN2 while PLIN4 was largely distributed in the cytosol. mRNA expression of PLIN2, but not PLIN1 or PLIN4, was increased by olanzapine. On the other hand, olanzapine did not alter the mRNA level of transcription regulators involved in adipocyte-differentiation or adipokines. The present study shows that olanzapine induced transient PLIN2 expression in hMSCs that could result in an accumulation of lipid droplets and overexpression of PLIN1 and PLIN4, providing information of possible interest for olanzapine-induced weight gain.

• Authors: Satomi Nimura, Tomohiro Yamaguchi, Koki Ueda, Karin Kadokura, Toshihiro Aiuchi, Rina Kato, Takashi Obama, Hiroyuki Itabe
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 467 Issue 4 Pg. 906-12 (Nov 27 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26471304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antipsychotic Agents
• Carrier Proteins
• PLIN1 protein, human
• Perilipin-1
• Phosphoproteins
• RNA, Messenger
• Transcription Factors
• Benzodiazepines
• Olanzapine

Topics

• Adipocytes (cytology, drug effects, metabolism)
• Antipsychotic Agents (pharmacology)
• Benzodiazepines (pharmacology)
• Carrier Proteins (metabolism)
• Cell Differentiation
• Cells, Cultured
• Dose-Response Relationship, Drug
• Humans
• Lipid Droplets (metabolism)
• Mesenchymal Stem Cells (cytology, drug effects)
• Olanzapine
• Perilipin-1
• Phosphoproteins (metabolism)
• RNA, Messenger (genetics)
• Transcription Factors (genetics)