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Role of PPARγ, transcriptional cofactors, and adiponectin in the regulation of nutrient metabolism, adipogenesis and insulin action: view from the chair

International Journal of Obesity volume 29, pages S3–S4 (2005)Cite this article

The peroxisome proliferator-activated receptors (PPARs) compose a nuclear receptor subfamily.1 The three PPAR isoforms, γ, α and δ, which are encoded by three separate genes, are nutrient sensors that regulate metabolic homeostasis. They are ligand-regulated transcription factors whose main physiological actions are mediated by altering gene expression. PPARs heterodimerize with RXR, then bind to peroxisome proliferator response elements in regulatory domains of genes. Upon being bound by agonists, PPAR conformation is changed such that it binds with high affinity to coactivators that remodel chromatin and communicate with the cellular transcriptional machinery. As a result, transcriptional initiation is induced and the levels of PPAR-responsive transcripts increase.

PPARγ is highly expressed in adipose tissue. Activation of PPARγ induces adipocyte differentiation and lipid accumulation by adipocytes by modulating numerous genes regulating adipogenesis, lipid uptake and lipid metabolism. Notably, PPARγ null cells cannot differentiate into adipocytes and the adipose-specific ablation of PPARγ results in adipocyte hypocellularity and reduced adiposity. Thiazolidinedione (TZD) insulin-sensitizing agents are PPARγ ligands; their antidiabetic efficacy in vivo has been shown to correlate with their receptor agonist potency. The insulin-sensitizing action of PPARγ agonists results from their ability to lower circulating free fatty acids by decreasing adipocyte lipolysis, regulate the expression of proteins that modulate insulin action and serve as adipose remodeling agents that direct lipids away from lipolytic visceral fat depots and into subcutaneous fat tissue containing small, insulin-responsive adipocytes.2

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  1. Department of Metabolic Disorders, Merck Research Laboratories, Rahway, NJ, USA

    J P Berger

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Correspondence to J P Berger.

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Berger, J. Role of PPARγ, transcriptional cofactors, and adiponectin in the regulation of nutrient metabolism, adipogenesis and insulin action: view from the chair. Int J Obes 29 (Suppl 1), S3–S4 (2005). https://doi.org/10.1038/sj.ijo.0802904

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