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J Biol Chem, Vol. 275, Issue 3, 1873-1877, January 21, 2000
Inhibits Adipocyte Differentiation*
§,
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From the While searching for natural ligands for the
peroxisome proliferator-activated receptor (PPAR) Dana-Farber Cancer Institute and Department
of Cell Biology, Harvard Medical School, ¶ Center for Experimental
Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham
and Women's Hospital and Harvard Medical School, Boston, Massachusetts
02115, and Biotechnology Laboratory, Sumitomo Chemical Company,
Takarazuka 665-8555, Japan
, we identified a
synthetic compound that binds to this receptor. Bisphenol A diglycidyl
ether (BADGE) is a ligand for PPAR with a
Kd(app) of 100 µM. This compound
has no apparent ability to activate the transcriptional activity of
PPAR; however, BADGE can antagonize the ability of agonist ligands
such as rosiglitazone to activate the transcriptional and adipogenic
action of this receptor. BADGE also specifically blocks the ability of
natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to
undergo hormone-mediated cell differentiation. These results provide
the first pharmacological evidence that PPAR activity is required
for the hormonally induced differentiation of adipogenic cells.
To whom correspondence should be addressed: Dana-Farber Cancer
Inst., 1 Jimmy Fund Way, Smith 958, Boston, MA 02115. Tel.: 617-632-3587; Fax: 617-632-4655; E-mail:
bruce_spiegelman@dfci.harvard.edu.
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