Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation

Mol Cell Biol. 2000 Jul;20(14):5343-9. doi: 10.1128/mcb.20.14.5343-5349.2000.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells / drug effects
  • 3T3 Cells / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / physiology*
  • Amino Acid Sequence
  • Angiopoietin-like 4 Protein
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Animals
  • Base Sequence
  • Blood Proteins*
  • Cell Differentiation / genetics
  • Cycloheximide / pharmacology
  • Female
  • Gene Expression Regulation
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Intercellular Signaling Peptides and Proteins
  • Leptin / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Molecular Sequence Data
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism*
  • Nutritional Physiological Phenomena
  • Pioglitazone
  • Placenta / physiology
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sequence Homology, Amino Acid
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • ANGPTL2 protein, human
  • Angiopoietin-like 4 Protein
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Angptl4 protein, mouse
  • Blood Proteins
  • Glycoproteins
  • Hypoglycemic Agents
  • Intercellular Signaling Peptides and Proteins
  • Leptin
  • Muscle Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Cycloheximide
  • Pioglitazone