MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN
Location: Children Nutrition Research Center (Houston, Tx)
Title: Tlr2 is critical for diet-induced metabolic syndrome in a murine model
| Himes, Ryan - |
| Smith, Wayne - |
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 1, 2009
Publication Date: October 19, 2009
Citation: Himes, R.W., Smith, W.C. 2009. Tlr2 is critical for diet-induced metabolic syndrome in a murine model. Journal of Federation of American Societies for Experimental Biology. 24(3):731-739.
Interpretive Summary: Metabolic syndrome is the name given to a complex of conditions consisting of obesity, diabetes, abnormal blood lipids, fatty liver, high blood pressure, and inflammation. It is associated with coronary artery disease and stroke. The incidence of this syndrome has been increasing in western societies in association with the obesity epidemic. The purpose of this study was to determine if a protein called Toll-Like Receptor 2 (TLR2) plays a role in development of the metabolic syndrome. TLR2 has been shown to be important in resistance to certain types of infection, but recent studies have suggested that inappropriate activation of this protein may cause chronic disease such as the metabolic syndrome. Inappropriate activation may occur as a result of excess fat in the diet. In this study, mice were fed diets high in either corn oil or milk fat and shown to develop many aspects of the metabolic syndrome. Mice genetically engineered to be deficient in TLR2 were fed these diets and found to have a markedly reduced metabolic syndrome. We concluded from these studies that TLR2 is necessary for the development of diet-induced metabolic syndrome.
Obesity and its associated comorbidities, termed metabolic syndrome, are increasingly prevalent, and they pose a serious threat to the health of individuals and populations. Gene-environment interactions have been scrutinized since the kinetics of the increased prevalence of obesity would argue against a purely genetic etiology. Toll-like receptors (TLRs), widely expressed and highly conserved transmembrane receptors, are at the intersection of diet and metabolism, and may therefore be important determinants of weight gain and its sequellae. We sought specifically to determine the role of Tlr2 in the development of obesity and metabolic syndrome utilizing two dietary models that approximate contemporary diet compositions. Using C57BL/6 Hsd mice (wild type, WT) and mice with a targeted mutation in Tlr2 (Tlr2(-)(/)(-)), we showed that mice lacking TLR2 are substantially protected from diet-induced adiposity, insulin resistance, hypercholesterolemia, and hepatic steatosis. In adipose tissue, Tlr2 deletion was associated with attenuation of adipocyte hypertrophy, as well as diminished macrophage infiltration and inflammatory cytokine expression.