Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Health Personnel/statistics & numerical data , Immunogenicity, Vaccine , Vaccines, Synthetic/immunology , Adult , Antibodies, Neutralizing/blood , BNT162 Vaccine , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , Female , Hong Kong/epidemiology , Humans , Immunoglobulin G/blood , Logistic Models , Male , Middle Aged , SARS-CoV-2 , Serologic Tests/methods , Serologic Tests/statistics & numerical data , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vaccines, Synthetic/administration & dosage , mRNA VaccinesSubject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Health Personnel/statistics & numerical data , Immunogenicity, Vaccine , Adult , Antibodies, Neutralizing/blood , BNT162 Vaccine , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Hong Kong/epidemiology , Humans , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2 , Serologic Tests/methods , Serologic Tests/statistics & numerical data , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , mRNA VaccinesABSTRACT
AIMS/HYPOTHESIS: Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised that the inflammatory signals transduced by TLR2 contribute to insulin resistance. METHODS: Mice deficient in TLR2 were used to investigate the in vivo roles of TLR2 in initiating and maintaining inflammation-associated insulin resistance and energy homeostasis. RESULTS: We first recapitulated the observation with elevated expression of TLR2 and inflammatory cytokines in white adipose tissue and liver of ob/ob mice. Aged or high-fat-fed TLR2-deficient mice were protected from obesity and adipocyte hypertrophy compared with wild-type mice. Moreover, mice lacking TLR2 exhibited improved glucose tolerance and insulin sensitivity regardless of feeding them regular chow or a high-fat diet. This is accompanied by reductions in expression of inflammatory cytokines and activation of extracellular signal-regulated kinase (ERK) in a liver-specific manner. The attenuated hepatic inflammatory cytokine expression and related signalling are correlated with increased insulin action specifically in the liver in TLR2-deficient mice, reflected by increased insulin-stimulated protein kinase B (Akt) phosphorylation and IRS1 tyrosine phosphorylation and increased insulin-suppressed hepatocyte glucose production. CONCLUSIONS/INTERPRETATION: The absence of TLR2 attenuates local inflammatory cytokine expression and related signalling and increases insulin action specifically in the liver. Thus, our work has identified TLR2 as a key mediator of hepatic inflammation-related signalling and insulin resistance.