Adiponectin: A relevant player in PPARγ-agonist-mediated improvements in hepatic insulin sensitivity?

The potent insulin-sensitizing effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists are well established. However, it is still a matter of intense debate as to which tissue(s) represent the most critical sites of action for PPARγ agonists, and what the relevant target genes are that ultimately mediate the improvements in insulin sensitivity. The cell type with the highest levels of PPARγ is the adipocyte, and as such the adipocyte is an excellent candidate cell to look for critical mediators of PPARγ agonist action. Adiponectin, an adipocyte-specific secretory protein, is upregulated in response to PPARγ agonist exposure, and its serum levels consequently increase significantly. Genetic, pharmacological and clinical studies have demonstrated potent insulin-sensitizing effects of adiponectin. Here, we summarize the evidence that implicates adiponectin as a critical mediator of PPARγ-agonist-mediated improvements in insulin sensitivity, particularly in the context of PPARγ-agonist-mediated enhancements of hepatic insulin sensitivity.