Depot specificities of PPARg ligand actions on lipid and glucose metabolism and their implication in PPARg-mediated body fat redistribution

Abstract

PPARγ is a ligand-activated nuclear receptor mainly expressed in white and brown adipose tissues where it controls adipocyte differentiation, metabolism, adipokine secretion and survival. PPARγ is specifically and potently activated by thiazolidinediones, a class of synthetic agonists that, owing to their beneficial effect on whole-body insulin sensitivity, are widely used in the treatment of insulin-resistant states, such as Type 2 diabetes and metabolic syndrome. In association with the improvement in whole-body glucose homeostasis, PPARγ activation by thiazolidinediones administration in both humans and rodents results in white and brown adipose tissue remodeling associated with lipid redistribution from visceral to subcutaneous fat depots. Directing fat away from visceral to subcutaneous fat depots may constitute one mechanism whereby PPARγ activation prevents the deleterious effects of visceral fat accumulation on the development of metabolic syndrome and the progression to cardiovascular disease. This review, addresses the mechanisms underlying the depot-specific actions of PPARγ ligand therapy on subcutaneous and visceral fat morphology, cellularity and metabolism that are likely involved in the fat redistribution induced in vivo by pharmacological PPARγ activation.

Keywords:

• adipose tissue remodeling
• apoptosis
• fat cell proliferation
• lipolysis
• preadipocyte differentiation
• rosiglitazone
• subcutaneous fat
• triacylglycerol synthesis
• visceral fat