Potential for peroxisome proliferator-activated receptor-gamma agonists in progression: beyond metabolism.

PURPOSE OF REVIEW: The thiazolidinediones are agonists for peroxisome proliferator-activated receptor-gamma, and promote insulin sensitization and improve dyslipidemia in patients with type II diabetes mellitus. Peroxisome proliferator-activated receptor-gamma transduces its actions by binding to common consensus response elements called peroxisome proliferator-activated receptor-response elements, thus modifying expression of numerous genes. Peroxisome proliferator-activated receptor-gamma is widely expressed, including in macrophages and vascular smooth muscle cells. I will review recent novel insights into peroxisome proliferator-activated receptor-gamma agonist actions.

RECENT FINDINGS: The thiazolidinediones have beneficial effects in humans with type II diabetes related in part to improvement of dysmetabolic syndrome, and also have beneficial effects on progressive renal damage in animal models of diabetic nephropathy and in models with severe hyperlipidemia. Peroxisome proliferator-activated receptor-gamma agonists also have direct benefits on progressive renal injury independent of altering the dysmetabolic profile.

SUMMARY: We will review selected evidence of actions of peroxisome proliferator-activated receptor-gamma agonists beyond metabolism, focusing on experimental work, and examine interactions with other key profibrotic mediators, including transforming growth factor-beta and the renin-angiotensin system.