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Molecular and Cellular Biology, July 2000, p. 5343-5349, Vol. 20, No. 14
Dana-Farber Cancer
Institute,1 and Department of Cell
Biology,2 Harvard Medical School, Boston,
Massachusetts 02115; Millennium Pharmaceuticals, Incorporated,
Cambridge, Massachusetts 021393; and
Laboratory of Molecular Genetics, Rockefeller University, New York,
New York 100214
Received 16 February 2000/Returned for modification 27 March
2000/Accepted 13 April 2000
The nuclear receptor peroxisome proliferator-activated receptor
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Peroxisome Proliferator-Activated Receptor
Target Gene Encoding a Novel Angiopoietin-Related Protein
Associated with Adipose Differentiation
regulates adipose differentiation and systemic insulin signaling via
ligand-dependent transcriptional activation of target genes. However,
the identities of the biologically relevant target genes are largely
unknown. Here we describe the isolation and characterization of a novel
target gene induced by PPAR
ligands, termed PGAR (for PPAR
angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction
of PGAR follows a rapid time course typical of immediate-early genes
and occurs in the absence of protein synthesis. The expression of PGAR
is predominantly localized to adipose tissues and placenta and is
consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of
the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of
systemic lipid metabolism or glucose homeostasis.
*
Corresponding author. Mailing address: Dana-Farber
Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: (617)
632-3567. Fax: (617) 632-4655. E-mail:
bruce_spiegelman{at}dfci.harvard.edu.
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