Objective To investigate the potential role of nucleotide-binding oligomerization domain 1(NOD1),a component of the innate immune system,in mediating lipid-induced insulin resistance in adipocytes.Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments.The effect of oleate/palmitate mixture on nuclear factor-κB(NF-κB)activation was analyzed by reporter plasmid assay.The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR.Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H]glucose uptake assay.Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA(siRNA)targeting NOD1 upon fatty acids treatment were analyzed.Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6,tumor necrosis factor-α,and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4,and these effects were blocked by siRNA targeting NOD1.Furthermore,saturated fatty acids decreased the ability of insulin-stimulated glucose uptake.Importantly,siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes,suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.
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