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Inhibition of adipose differentiation by phosphatidylinositol 3‐kinase inhibitors
Author(s) -
Xia Xianmin,
Serrero Ginette
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199901)178:1<9::aid-jcp2>3.0.co;2-#
Subject(s) - adipogenesis , wortmannin , phosphatidylinositol , kinase , adipose tissue , ly294002 , microbiology and biotechnology , cellular differentiation , biology , 3t3 l1 , chemistry , endocrinology , biochemistry , gene
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) γ, a master regulator in adipogenesis induced during the differentiation process, was also examined. LY294002 significantly inhibited the induction of PPARγ mRNA expression. During the initiation phase of adipogenesis (day 4 to day 6), the expression of PPARγ was induced and LY294002 blocked the increase of expression of PPARγ mRNA. The inhibition of expression of PPARγ may provide a molecular mechanism for the action of PI 3‐kinase inhibitors on adipose differentiation. J Cell Physiol 178:9–16, 1999. © 1999 Wiley‐Liss, Inc.