Tlr2 is critical for diet‐induced metabolic syndrome in a murine model

Abstract

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.-Himes, R. W., Smith, C. W. Tlr2 is critical for diet-induced metabolic syndrome in a murine model.

Innate immunity in diabetes and diabetic nephropathy

“…Mice lacking Tlr2 are substantially protected from diet-induced adiposity, insulin resistance, hypercholesterolaemia, hepatic steatosis, and macrophage infiltration, and the level of inflammatory cytokines are reduced compared to wild-type mice 52,53 . Furthermore, the absence of TLR2 was shown to attenuate local inflammatory cytokine expression and enhance insulin action in the liver 54 .…”

“…[H1] T2DM, insulin resistance, and obesity Subclinical and chronic inflammation in obesity and metabolic syndrome can induce insulin resistance and T2DM, and T2DM associated with obesity is now considered as an inflammatory chronic disease 49 Mice lacking Tlr2 are substantially protected from diet-induced adiposity, insulin resistance, hypercholesterolaemia, hepatic steatosis, and macrophage infiltration, and the level of inflammatory cytokines are reduced compared to wild-type mice 52,53 . Furthermore, the absence of TLR2 was shown to attenuate local inflammatory cytokine expression and enhance insulin action in the liver 54 .…”

Impact of the Gut Microbiota on the Development of Obesity: Current Concepts

“…Transfer of the gut microbiota from TLR5-defi cient mice to wild-type, germ-free mice conferred features of the metabolic syndrome. In contrast, abrogation of the expression of TLR2, which recognizes a number of microbial products including peptidoglycan, lipoteichoic acid, and lipoprotein, protects mice from diet-induced adiposity, insulin resistance, hypercholesterolemia, and hepatic steatosis and is also associated with attenuation of adipocyte hypertrophy ( 30 ). Notably, members of the phyla Bacteroidetes , Proteobacteria , and Actinobacteria were more abundant in mutant mice than in wild-type mice ( 31 ), consistent with previous studies suggesting that the relative proportion of Bacteroidetes is reduced in obese mice ( 8 ).…”

The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation*

“…These data support the notion that fatty acid intake may have a strong impact on bone metabolism. TLRs were recently shown to bind saturated fatty acid (10) and to be involved in fatty-acid induced insulin resistance (11)(12)(13). Relevant to bone metabolism, mice deficient for TLR4 exhibit increased bone size with increased bone mineral content and density (14).…”