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Molecular and Cellular Biology, July 2000, p. 5343-5349, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Peroxisome Proliferator-Activated Receptor gamma  Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation

J. Cliff Yoon,1,2 Troy W. Chickering,3 Evan D. Rosen,1,2 Barry Dussault,3 Yubin Qin,3 Alexander Soukas,4 Jeffrey M. Friedman,4 William E. Holmes,3 and Bruce M. Spiegelman1,2,*

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 gamma  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 PPARgamma ligands, termed PGAR (for PPARgamma 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.

Molecular and Cellular Biology, July 2000, p. 5343-5349, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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