Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes
Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study,...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861317300051 |
| _version_ | 1818498325705392128 |
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| author | Tomomi Tsubai Akira Yoshimi Yoji Hamada Makoto Nakao Hiroshi Arima Yutaka Oiso Yukihiro Noda |
| author_facet | Tomomi Tsubai Akira Yoshimi Yoji Hamada Makoto Nakao Hiroshi Arima Yutaka Oiso Yukihiro Noda |
| author_sort | Tomomi Tsubai |
| collection | DOAJ |
| description | Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors 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. |
| first_indexed | 2024-12-10T18:56:45Z |
| format | Article |
| id | doaj.art-1b01c9892002459b9236659a802e4eda |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T18:56:45Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-1b01c9892002459b9236659a802e4eda2022-12-22T01:37:07ZengElsevierJournal of Pharmacological Sciences1347-86132017-02-011332798710.1016/j.jphs.2017.01.004Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytesTomomi Tsubai0Akira Yoshimi1Yoji Hamada2Makoto Nakao3Hiroshi Arima4Yutaka Oiso5Yukihiro Noda6Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDivision of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, JapanCollege of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya 463-8521, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, JapanDivision of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanClozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT2C and histamine H1 receptors 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.http://www.sciencedirect.com/science/article/pii/S1347861317300051ClozapineBlonanserinLeptin3T3-L1 adipocyteMetabolic syndrome |
| spellingShingle | Tomomi Tsubai Akira Yoshimi Yoji Hamada Makoto Nakao Hiroshi Arima Yutaka Oiso Yukihiro Noda Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes Journal of Pharmacological Sciences Clozapine Blonanserin Leptin 3T3-L1 adipocyte Metabolic syndrome |
| title | Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes |
| title_full | Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes |
| title_fullStr | Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes |
| title_full_unstemmed | Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes |
| title_short | Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes |
| title_sort | effects of clozapine on adipokine secretions productions and lipid droplets in 3t3 l1 adipocytes |
| topic | Clozapine Blonanserin Leptin 3T3-L1 adipocyte Metabolic syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S1347861317300051 |
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