Review: Peroxisome proliferator-activated receptor gamma and adipose tissue--understanding obesity-related changes in regulation of lipid and glucose metabolism.
BACKGROUND
Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation).


METHODS
Articles on the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990-2006).


RESULTS
Articles were assessed to provide a comprehensive overview of how PPARgamma-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis.


CONCLUSIONS
PPARgamma is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and adipocyte phenotype and up-regulates genes involved in fatty acid metabolism and triglyceride storage. Furthermore, PPARgamma activation is associated with potentially beneficial effects on the expression and secretion of a range of factors, including adiponectin, resistin, IL-6, TNFalpha, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and angiotensinogen, as well as a reduction in plasma nonesterified fatty acid supply. The effects of PPARgamma also extend to macrophages, where they suppress production of inflammatory mediators. As such, PPARgamma activation appears to have a beneficial effect on the relationship between the macrophage and adipocyte that is distorted in obesity. Thus, PPARgamma-activating ligands improve adipose tissue function and may have a role in preventing progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.
Sharma
Arya M
AM
Canada Research Chair for Cardiovascular Obesity Research and Management, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2. sharma@cardio.on.ca
Staels
Bart
B
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D047495:PPAR gamma / Q000378:metabolism*
D047495:PPAR gamma; D005947:Glucose