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.
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.
Caricilli
Andréa M
AM
Department of Internal Medicine, State University of Campinas, 13081-970 Campinas, SP, Brazil.
Nascimento
Paula H
PH
Pauli
José R
JR
Tsukumo
Daniela M L
DM
Velloso
Lício A
LA
Carvalheira
José B
JB
Saad
Mário J A
MJ
D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004041:Dietary Fats / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015151:Immunoblotting; D047468:Immunoprecipitation; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020319:Oligodeoxyribonucleotides, Antisense; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2