Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells
Journal
Pharmacological Research
Journal Volume
56
Journal Issue
3
Pages
202-208
Date Issued
2007
Author(s)
Abstract
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.
Subjects
3T3-L1; Adipogenesis; Fatty acid synthase; Olanzapine; SREBP-1
Other Subjects
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
Type
journal article