Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet

Abstract

The aims of the present study were to investigate the expression of toll-like receptor 2 (TLR2) in muscle and white adipose tissue (WAT) of diet-induced obesity (DIO) mice, and also the effects of its inhibition, with the use of TLR2 antisense oligonucleotide (ASON), on insulin sensitivity and signaling. The expression of TLR2 was increased in muscle and WAT of DIO mice, compared with those that received standard chow. Inhibition of TLR2 in DIO mice, by TLR2 ASON, improved insulin sensitivity and signaling in muscle and WAT. In addition, data show that the inhibition of TLR2 expression prevents the activation of IKBKB, MAPK8, and serine phosphorylation of IRS1 in DIO mice, suggesting that TLR2 is a key modulator of the crosstalk between inflammatory and metabolic pathways. We, therefore, suggest that a selective interference with TLR2 presents an attractive opportunity for the treatment of insulin resistance in obesity and type 2 diabetes.

Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet

“…Reduced adiposity and reduced hepatosteatosis were also consistent with overall improvements in whole body and hepatic insulin sensitivity as determined by the hyperinsulinaemic-euglycaemic clamp. Thus, our data show for the first time that TLR2 regulates hepatic insulin sensitivity during HFD, extending findings that reduced TLR2 expression by antisense oligonucleotides improved insulin signalling in muscle and white adipose tissue of HFD-fed mice [32]. [12].…”

The expression of genes involved in NF-κB activation in peripheral blood mononuclear cells of patients with gestational diabetes

“…In addition to host defense against foreign pathogens, recent studies implicate a role of NF-kB (7,8,9,10,11) and TLR pathway (10,12,13,14,15,16,17,18,19,20) in the pathogenesis of obesity-and type 2 diabetesrelated insulin resistance and metabolic disturbances. Moreover, de Mello et al (10,11) demonstrated that in patients with the metabolic syndrome, the changes in insulin resistance were associated with the changes in the expression of genes involved in the NF-kB signaling pathways in peripheral blood mononuclear cells (PBMCs).…”

Translational research into gut microbiota: new horizons on obesity treatment: updated 2014

“…A short time ago, several studies highlighted a correlation between type-2 diabetes and obesity which a state of subclinical chronic inflammation in several tissues such as the adipose tissue, liver and hypothalamus (40)(41)(42)(43)(44). Based on this observation, a new hypothesis has been proposed correlating intestinal flora and obesity (Figure 2).…”