Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells

International Journal of Molecular Sciences

Bo Kyung Sun²  Ji Hye Kim²  Joon-Seok Choi¹  Sung-Joo Hwang²  Jong-Hyuk Sung² 

[1] College of Pharmacy, Catholic University of Daegu, Daegu 712-702, Korea; E-Mail:;College of Pharmacy, Yonsei University, Incheon 406-840, Korea; E-Mails:

关键词: adipose-derived stem cells;    fluoxetine;    autophagy;    proliferation;    adipogenic differentiation;   

DOI  :  10.3390/ijms160716655

来源: mdpi

【 摘 要 】

Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs) or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.