title: 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.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Nimura
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Karin
authors.initials: K
authors.lastname: Kadokura
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aiuchi
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Kato
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Obama
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: h-itabe@pharm.showa-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D000077152:Olanzapine; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D002352:Carrier Proteins; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Human adipocytes; Lipid droplets; Olanzapine; PLIN2; PLIN4; Weight gain