Evidence for an effect of clozapine on the regulation of fat-cell derived factors.
OBJECTIVE
The aims of this study were to investigate the effects of clozapine on adipocyte differentiation and its regulation for fat-cell derived factors.


METHODS
3T3-L1 preadipocytes were induced into differentiated adipocytes by the addition of 5 microg/ml of insulin, 1 micromol/l dexamethasone, 10 mmol/l IBMX, 1% DMSO, and 10% FBS in DMEM medium. The semi-quantitative RT-PCR was performed to determine the mRNA levels of PPAR gamma, C/EBP alpha, ADD1/SREBP(1C), LPL, and DGAT1. The expression levels of LPL and DGAT1 proteins in the adipocytes treated with clozapine or rosiglitazone were determined by Western blot analysis. The triglyceride concentration was determined by use of GPO-POD assay Kit.


RESULTS
Clozapine enhanced the expression level of ADD1/SREBP(1C) mRNA and triglyceride concentration in the differentiated adipocytes. Clozapine significantly suppressed the expression levels of LPL mRNA and LPL protein with a dose-dependent and time-dependent manner, respectively.


CONCLUSIONS
These data suggest that clozapine might play an important role in inducing adipocyte differentiation and the regulation of fat-cell derived factors.
Yang
Zhi
Z
Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University Xiangya School of Medicine, Changsha, Hunan 410078, PR China.
Yin
Ji-Ye
JY
Gong
Zhi-Cheng
ZC
Huang
Qiong
Q
Chen
Hao
H
Zhang
Wei
W
Zhou
Hong-Hao
HH
Liu
Zhao-Qian
ZQ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D012333:RNA, Messenger; D014280:Triglycerides; D003024:Clozapine