HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: 297/6/E1378    most recent ajpendo.00252.2009v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, M. Articles by Zhang, S. X PubMed PubMed Citation Articles by Wang, M. Articles by Zhang, S. X

RESEARCH ARTICLE

Pigment Epithelium-derived factor (PEDF) suppresses adipogenesis via inhibition of the MAPK/ERK pathway in 3T3-L1 preadipocytes

¹University of Oklahoma Health Sciences Center

Submitted 20 April 2009 ; revised 3 September 2009 ; accepted in final form 30 September 2009

Aims. We previously reported that circulating levels of pigment epithelium-derived factor (PEDF), a newly identified adipokine, are increased in patients with type 2 diabetes, correlating with body mass index. However, the role of PEDF in adipogenesis remains elusive. In the present study, we have investigated the effects and mechanisms of PEDF on adipocyte differentiation in 3T3-L1 preadipocytes. Methods. Differentiation of 3T3-L1 preadipocytes was induced in the presence or absence of human recombinant PEDF protein. The effects of PEDF on adipogenic gene expression, mitotic clonal expansion (MCE), and MAPK activation were investigated. Results. Physiological concentrations of human PEDF protein inhibited adipocyte differentiation, evidenced by decreased lipid accumulation, down-regulation of adipocyte markers, and inhibition of master adipogenic transcription factors, such as C/EBP- and PPAR-. The anti-adipogenic effects of PEDF were observed only when PEDF was added to the cells at day 0, but not at day 3 during differentiation, suggesting that PEDF targets some early adipogenic events. Similarly, over-expression of PEDF by adenovirus attenuated adipocyte differentiation. Further studies revealed that PEDF, or U0126, a specific MAPK/ERK inhibitor, sequentially inhibited the early activation of ERK and MCE. Moreover, PEDF attenuated expression and the phosphorylation of C/EBP-β at Thr188, an essential step for transcriptional activation of C/EBP-β. In addition, PEDF expression was significantly decreased in the first 24 h during adipocyte differentiation, suggesting that down-regulation of PEDF may be essential for the initiation of MCE and adipogenesis. Conclusions. PEDF inhibits adipogenesis in 3T3-L1 preadipocytes, partially due to inhibition of the MAPK/ERK signaling pathway and MCE.

PEDF; adipogenesis