Tartrate-resistant acid phosphatase type 5/ACP5 promotes cell cycle entry of 3T3-L1 preadipocytes by increasing IGF-1/Akt signaling.

Abstract

Tartrate-resistant acid phosphatase (TRAP, encoded by ACP5)-overexpressing mice exhibit hyperplastic obesity. As the molecular mechanism remains elusive, the aims were to characterize the effect of TRAP on preadipocyte proliferation. We investigated cell cycle entry and signal transduction, that is, insulin-like growth factor 1 (IGF-1)/ insulin receptor substrate 1 (IRS-1) and the Akt signaling pathways, in 3T3-L1 preadipocytes treated with the TRAP 5a isoform. Results show that TRAP 5a increases S-phase entry. TRAP 5a stimulation increases IGF-1 mRNA and IRS-1 activation, indicative of insulin-like growth factor 1 receptor (IGF1R) activation. Furthermore, TRAP 5a stimulation resulted in Akt signaling pathway activation and subsequent increased nuclear translocation of β-catenin. In conclusion, TRAP 5a increases proliferation of preadipocytes in a dose-dependent fashion by promoting entry into S-phase. Part of this effect is likely due to increased IGF-1 signaling through the Akt signaling pathway.