Toll-like receptor 2 deficiency ameliorates obesity-induced cardiomyopathy via inhibiting NF-B signaling pathway

Growing evidence demonstrates that chronic low-grade inflammation, which is induced by high -fat diet (HFD) or saturated fatty acid, plays an important role in the obesity -induced cardiomyopathy (OIC) process. Moreover, obesity is associated with the activation of different inflammatory pathways, including nuclear factor-kappa B (NF-kappa B), Toll -like -receptor -2 (TLR2) and Toll -like -receptor -4 (TLR4). In this study, we established an HFD-induced cardiac injury mouse model and palmitate (PA) -induced myocardial cell model to evaluate the role of TLR2 in OIC. Our data show that TLR2 blockade using TLR2 knockout (KO) mice or a TLR2-specific inhibitor, C29, markedly ameliorated HFD- or PA -induced inflammation, myocardial fibrosis, and hypertrophy both in vivo and in vitro. Moreover, the PA -induced myocardial cell injury was mediated via inducing the formation of TLR2-MyD88 complex in a TLR4-independent manner in cardiomyocytes. Our data prove the critical role of cardiac TLR2 in the pathogenesis of HFD- and saturated fatty acid -induced myocarditis, fibrosis, myocardial hypertrophy, and cardiac dysfunction. Inhibition of TLR2 pathway may be a therapeutic strategy of OIC.