Inhibition of adipose differentiation by phosphatidylinositol 3-kinase inhibitors

✍ Scribed by Xianmin Xia; Ginette Serrero

• Book ID: 101259680
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 238 KB
• Volume: 178
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199901)178:1<9::aid-jcp2>3.0.co;2-#

✦ Synopsis

Phosphatidylinositol (PI) 3-kinase plays an important role in various cellular signaling mechanisms in several cell systems. The role of PI 3-kinase in adipose differentiation was investigated. For this purpose, we examined the effect of specific inhibitors of PI 3-kinase on the differentiation of two adipogenic cell lines, 1246 and 3T3-L1. The results show that two structurally different inhibitors of PI 3-kinase, i.e., LY294002 and wortmannin, blocked adipose differentiation in a time and dose-dependent fashion. The results from time-course studies indicated that PI 3-kinase activity is most important in the early phase (day 4 to day 6) of the differentiation program. The effect of PI 3-kinase inhibitor on the expression of the peroxisome proliferator-activated receptor (PPAR) ␥, a master regulator in adipogenesis induced during the differentiation process, was also examined. LY294002 significantly inhibited the induction of PPAR␥ mRNA expression. During the initiation phase of adipogenesis (day 4 to day 6), the expression of PPAR␥ was induced and LY294002 blocked the increase of expression of PPAR␥ mRNA. The inhibition of expression of PPAR␥ may provide a molecular mechanism for the action of PI 3-kinase inhibitors on adipose differentiation.