The insulin/insulin-like growth factor 1 (IGF-1) signaling pathway is a major regulator of adipose tissue growth and differentiation. We recently demonstrated that human protein tyrosine phosphatase (PTP) L1, a large cytoplasmic phosphatase also known as PTP-BAS/PTPN13/PTP-1E, is a negative regulator of IGF-1R/IRS-1/Akt pathway in breast cancer cells. This triggered us to investigate the potential role of PTPL1 in adipogenesis. To evaluate the implication of PTP-BL, the mouse orthologue of PTPL1, in adipose tissue biology, we analyzed PTP-BL mRNA expression in adipose tissue in vivo and during proliferation and differentiation of 3T3-L1 pre-adipocytes. To elucidate the role of PTP-BL and of its catalytic activity during adipogenesis we use siRNA techniques in 3T3-L1 pre-adipocytes, and mouse embryonic fibroblasts that lack wildtype PTP-BL and instead express a variant without the PTP domain (Delta P/Delta P MEFs). Here we show that PTP-BL is strongly expressed in white adipose tissue and that PTP-BL transcript and protein levels increase during proliferation and differentiation of 3T3-L1 pre-adipocytes. Strikingly, knockdown of PTP-BL expression in 3T3-L1 adipocytes caused a dramatic decrease in adipogenic gene expression levels (PPAR gamma, aP2) and lipid accumulation but did not interfere with the insulin/Akt pathway. Delta P/Delta P MEFs differentiate into the adipogenic lineage as efficiently as wildtype MEFs. However, when expression of either PTP-BL or PTP-BL Delta P was inhibited a dramatic reduction in the number of MEF-derived adipocytes was observed. These findings demonstrate a key role for PTP-BL in 3T3-L1 and MEF-derived adipocyte differentiation that is independent of its enzymatic activity.
Downregulation of protein tyrosine phosphatase PTP-BL represses adipogenesis
Glondu-Lassis, M.; Dromard, M.; Chavey, C.; Puech, C.; Fajas, L.; Hendriks, W.; Freiss, G.
Int J Biochem Cell Biol
2009-11 / vol 41 / pages 2173-80
S1357-2725(09)00121-6 [pii] 10.1016/j.biocel.2009.04.004
1878-5875 (Electronic) 1357-2725 (Linking)
Animals; Cell Proliferation; Mice; Cell Differentiation; Gene Expression Regulation, Enzymologic; Gene Knockdown Techniques; 3T3-L1 Cells; Adipocytes/cytology/enzymology; Adipogenesis/*genetics; Clone Cells; Down-Regulation/*genetics; inhibitors/*genetics/metabolism; Protein Tyrosine Phosphatase, Non-Receptor Type 13/antagonists &