Both studies utilized large-scale gene expression analysis and histological evidence to compare the differences in gene expression in multiple tissues of both lean mice and mice of varying degrees of obesity. They found that the largest class of genes significantly regulated in obesity consists of macrophage and inflammatory genes in fatty tissue. Anthony Ferrante, Jr., and colleagues provide evidence that macrophage infiltration of adipose tissue is characteristic of human obesity, by demonstrating that body mass index and average fat cell size were significant predictors of macrophage accumulation in adipose tissue.
Hong Chen and colleagues demonstrated that the upregulation of many inflammation and macrophage-specific genes precedes a dramatic increase in circulating insulin levels and treatment with an insulin-sensitizing drug triggered downregulation of these genes. The data suggests that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.
In an accompanying commentary, Kathryn Wellen and Gökhan Hotamisligil from the Harvard School of Public Health discuss the inflammation of obese adipose tissue. While it remains to be shown how the inflammatory response in fatty tissue causes insulin resistance, these two studies prompt consideration of new models of the molecular changes that occur in fatty tissue in obesity in which macrophages play a major role.
TITLE: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance
Novartis Institutes for Biomedical Research Inc., Cambridge, Massachusetts, USA.
View the PDF of this article at: http://www.jci.org/cgi/content/full/112/12/1821
TITLE: Obesity is associated with macrophage accumulation in adipose tissue
Anthony W. Ferrante, Jr.
The Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Obesity-induced inflammatory changes in adipose tissue
Gökham S. Hotamisligil
Harvard School of Public Health, Boston, Massachusetts, USA.