title: Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes.
abstract: Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2Cand histamine H1receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT2C, but not a histamine H1, receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement.
authors.affiliation: Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan; College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya 463-8521, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tsubai
authors.affiliation: Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshimi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya 463-8521, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.affiliation: Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. Electronic address: ynoda@meijo-u.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Noda
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology; D002470:Cell Survival; D003024:Clozapine / Q000009:adverse effects* / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D051379:Mice; D010879:Piperazines / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D020738:Leptin; D010879:Piperazines; D010880:Piperidines; C079310:blonanserin; D003024:Clozapine
keywords: 3T3-L1 adipocyte; Blonanserin; Clozapine; Leptin; Metabolic syndrome