https://scholars.lib.ntu.edu.tw/handle/123456789/533355
標題: | Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells | 作者: | Yang L.-H. Chen T.-M. Yu S.-T. YEN-HUI CHEN |
關鍵字: | 3T3-L1; Adipogenesis; Fatty acid synthase; Olanzapine; SREBP-1 | 公開日期: | 2007 | 卷: | 56 | 期: | 3 | 起(迄)頁: | 202-208 | 來源出版物: | Pharmacological Research | 摘要: | Olanzapine is a second-generation atypical antipsychotic drug (AAPD). Major side effects of olanzapine are weight gain and development of diabetes mellitus, which are risk factors of cardiovascular diseases. The possible causes of metabolic adverse effects are known as poor satiety and increased food intake due to blockade of receptors such as 5-HT2C in CNS. In this study, we examine the effect of olanzapine on peripheral adipogenesis using cultured 3T3-L1 cell model. Olanzapine increased triacylglyceride (TG) accumulation during 3T3-L1 preadipocyte differentiation to mature adipocyte phenotype. TG accumulation was accompanied by overexpression of fatty acid synthase and adiponectin that are the downstream genes of sterol regulatory element binding protein-1 (SREBP-1), one of the key transcription factors in lipid homeostasis. We further consisted that mostly SREBP-1 and at a lesser extent peroxisome proliferator-activated receptor gamma (PPAR-γ), but not CCAAT/enhancer binding protein-α (C/EBP-α), were overexpressed and activated in 3T3-L1 adipocytes exposed to olanzapine. Furthermore, we showed that olanzapine enhanced the activity of SRE-1-containing LDLR promoter in transfected 3T3-L1 adipocytes and HepG2 cells. Taken together, olanzapine may cause body weight gain not only through influencing CNS receptors, but also affecting the peripheral adipogenesis regulated by SREBP-1. ? 2007 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548208771&doi=10.1016%2fj.phrs.2007.05.007&partnerID=40&md5=f29f81b2d1cf1e7fef926779f4d5abb8 https://scholars.lib.ntu.edu.tw/handle/123456789/533355 |
ISSN: | 10436618 | DOI: | 10.1016/j.phrs.2007.05.007 | SDG/關鍵字: | adiponectin; carbamazepine; CCAAT enhancer binding protein alpha; fatty acid synthase; imipramine; olanzapine; peroxisome proliferator activated receptor gamma; pioglitazone; sterol regulatory element binding protein 1; thioridazine; transcription factor; triacylglycerol; valproic acid; adipogenesis; animal cell; article; cancer cell culture; cell differentiation; cell maturation; cell strain 3T3; controlled study; downstream processing; gene overexpression; homeostasis; human; human cell; mouse; nonhuman; nucleotide sequence; phenotype; priority journal; promoter region; 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Antipsychotic Agents; Benzodiazepines; Cell Line, Tumor; Fatty Acid Synthetase Complex; Gene Expression Regulation; Hepatocytes; Humans; Mice; Phenotype; PPAR gamma; Promoter Regions (Genetics); Receptors, LDL; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transfection; Triglycerides; Up-Regulation; Weight Gain |
顯示於: | 臨床藥學研究所 |
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