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Thiazolidinedione derivatives are antidiabetic agents that
increase the insulin sensitivity of target tissues in animal models of
non-insulin-dependent diabetes mellitus. In vitro,
thiazolidinediones promote adipocyte differentiation of preadipocyte
and mesenchymal stem cell lines; however, the molecular basis for this
adipogenic effect has remained unclear. Here, we report that
thiazolidinediones are potent and selective activators of peroxisome
proliferator-activated receptor
Volume 270,
Number 22,
Issue of June 2, pp. 12953-12956, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
(PPAR
)
(PPAR
), a member of the
nuclear receptor superfamily recently shown to function in
adipogenesis. The most potent of these agents, BRL49653, binds to
PPAR
with a K
of approximately 40
nM. Treatment of pluripotent C3H10T1/2 stem cells with
BRL49653 results in efficient differentiation to adipocytes. These data
are the first demonstration of a high affinity PPAR ligand and provide
strong evidence that PPAR
is a molecular target for the adipogenic
effects of thiazolidinediones. Furthermore, these data raise the
intriguing possibility that PPAR
is a target for the therapeutic
actions of this class of compounds.
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