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Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated
J C Yoon1, T W Chickering, E D Rosen
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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.
Insights
Researchers identified a new gene, PPARgamma angiopoietin related (PGAR), regulated by PPARgamma. PGAR is rapidly induced in adipose tissue and may play a role in lipid and glucose homeostasis.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor crucial for regulating adipose differentiation and insulin signaling.
- The specific target genes activated by PPARgamma, which mediate its biological functions, remain largely unidentified.
Purpose of the Study:
- To identify and characterize novel PPARgamma target genes involved in metabolic regulation.
- To investigate the role of a newly discovered gene, PGAR, in adipogenesis and systemic metabolism.
Main Methods:
- Isolation and characterization of a novel PPARgamma-induced gene, PGAR.
- Analysis of PGAR transcriptional induction kinetics and its dependence on protein synthesis.
- Examination of PGAR expression patterns in various tissues and under different physiological conditions (obesity, nutrition, leptin administration).
Main Results:
- A novel gene, PGAR (PPARgamma angiopoietin related), was identified as a direct target of PPARgamma.
- PGAR exhibits rapid, immediate-early gene kinetics and is induced ligand-dependently by PPARgamma.
- PGAR expression is predominantly found in adipose tissue and placenta, and is upregulated in obesity models.
- Adipocyte differentiation, nutritional status, and leptin signaling modulate PGAR expression.
Conclusions:
- PGAR is a novel angiopoietin family member rapidly induced by PPARgamma signaling.
- The expression pattern and regulation of PGAR suggest a potential role in systemic lipid metabolism and glucose homeostasis.