Transglutaminase 2 (TG2) is a multifunctional enzyme with many biological functions. One of its prominent functions is to ensure effective clearance of apoptotic cells. Loss of TG2 was shown to sensitize for various chronic inflammatory diseases such as atherosclerosis and autoimmunity. There is an increasing amount of evidence to show that defective clearance of dying cells leads to the development of chronic systemic inflammatory diseases. Obesity is characterized by chronic low- grade inflammation. It is recognized that this chronic inflammatory state is involved in the pathogenesis of obesity-related insulin resistance, metabolic syndrome and type 2 diabetes.
In this study, we investigated the effects of the loss of TG2 on the development of obesity and insulin resistance. We performed a 17-week long feeding experiment in which TG2 KO mice and their wild type counterparts were fed with either normal or high fat diet. Our preliminary results indicate that the loss of TG2 in mice predisposes them to developing obesity and subsequent insulin resistance. The inflammatory markers and the characteristics of adipose tissue associated macrophages of these mice are under investigation.
This study was supported by grants from the National Research Fund (OTKA T104228 and 105046).