title: Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Yoon
authors.forename: T W
authors.initials: TW
authors.lastname: Chickering
authors.forename: E D
authors.initials: ED
authors.lastname: Rosen
authors.forename: B
authors.initials: B
authors.lastname: Dussault
authors.forename: Y
authors.initials: Y
authors.lastname: Qin
authors.forename: A
authors.initials: A
authors.lastname: Soukas
authors.forename: J M
authors.initials: JM
authors.lastname: Friedman
authors.forename: W E
authors.initials: WE
authors.lastname: Holmes
authors.forename: B M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology*; D000595:Amino Acid Sequence; D000091302:Angiopoietin-Like Protein 2; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins; D002454:Cell Differentiation / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D009747:Nutritional Physiological Phenomena; D000077205:Pioglitazone; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C485792:ANGPTL2 protein, human; D000091302:Angiopoietin-Like Protein 2; D000075803:Angiopoietin-Like Protein 4; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001798:Blood Proteins; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009124:Muscle Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D003513:Cycloheximide; D000077205:Pioglitazone