title: Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human Adipose-Derived Stem Cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Yonsei University, Incheon 406-840, Korea. bksun2011@gmail.com.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Yonsei University, Incheon 406-840, Korea. wisdom-ks@hanmail.net.|STEMORE Co., Ltd., Incheon 406-840, Korea. wisdom-ks@hanmail.net.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Daegu 712-702, Korea. joonschoi@naver.com.
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yonsei University, Incheon 406-840, Korea. sjh11@yonsei.ac.kr.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Yonsei University, Incheon 406-840, Korea. brian99@empal.com.|STEMORE Co., Ltd., Incheon 406-840, Korea. brian99@empal.com.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D049109:Cell Proliferation; D002478:Cells, Cultured; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D005473:Fluoxetine; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes
keywords: adipogenic differentiation; adipose-derived stem cells; autophagy; fluoxetine; proliferation