PPARγ activation rapidly induces PGAR, a novel angiopoietin-related secreted protein expressed predominantly in adipose tissue that is elevated in genetic models of obesity.
The identification of PGAR as a PPARgamma target gene provides a novel potential mechanism for the regulation of systemic lipid metabolism and glucose homeostasis.
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.
Yoon et al. (Sat,) conducted a other in Adipose differentiation and obesity (preclinical). PPARγ ligands (pioglitazone) and Leptin vs. Vehicle / PBS control was evaluated on PGAR gene expression and characterization. PPARγ activation rapidly induces PGAR, a novel angiopoietin-related secreted protein expressed predominantly in adipose tissue that is elevated in genetic models of obesity.
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