Review: Peroxisome proliferator-activated receptor gamma and adipose tissue--understanding obesity-related changes in regulation of lipid and glucose metabolism

J Clin Endocrinol Metab. 2007 Feb;92(2):386-95. doi: 10.1210/jc.2006-1268. Epub 2006 Dec 5.

Abstract

Context: 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).

Evidence acquisition: 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).

Evidence synthesis: 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.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Glucose / metabolism*
  • Humans
  • Lipid Metabolism / physiology*
  • Obesity / metabolism*
  • Obesity / physiopathology
  • PPAR gamma / metabolism*

Substances

  • PPAR gamma
  • Glucose