The nuclear receptor peroxisome proliferator-activated receptor ␥ 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.The past several years have witnessed an increasing recognition of the adipocyte as a remarkably dynamic entity that uses diverse signaling pathways to interact with other tissues. A compelling body of evidence now implicates adipocyte-derived proteins such as leptin (25a, 31) and tumor necrosis factor ␣ (10) as endocrine and/or autocrine modulators of distant and local targets. This enables the adipose tissue to exercise feedback regulation over systemic energy homeostasis and metabolism.In parallel with the improved functional understanding of the adipocyte, there has been a burgeoning interest in studying the molecular control of adipose differentiation. Research efforts directed at the transcriptional regulation of adipogenesis have led to the elucidation of several transcription factors that play key roles in this process, including the peroxisome proliferator-activated receptor ␥ (PPAR␥) (26) and the CCAAT/ enhancer binding protein (6) family members. PPAR␥, a member of the PPAR subfamily of nuclear hormone receptors, is a ligand-dependent transcription factor expressed in a tissueselective manner, with the highest levels in the adipose tissue. Much evidence from gain-and loss-of-function studies indicates that PPAR␥ is a central regulator of adipogenesis and systemic insulin action (reviewed in references 15 and 24), providing a crucial link between these two major aspects of adipocyte biology. PPAR␥ has been demonstrated to stimulate adipose conversion in a variety of fibroblastic cell lines ectopically expressing PPAR␥, as well as in preadipocyte and mesenchymal precursor cell lines (26). Committed myoblasts stably infected with PPAR␥ and CCAAT/enhancer binding protein ␣ can be induced to undergo transdifferentiation into adipocytes upon PPAR␥ activation (11). More recently, lossof-function experiments using PPAR␥ Ϫ/Ϫ mice or embryonic stem cells have confirmed the requirement of PPAR␥ f...

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