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. 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 combat 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 fatty acid treatment analyzed. Results Oleate / palmitate mixture activated the NF- 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. Implantantly, siRNA targeting NOD1 reversed suppression fatty acid-induced suppression of insulin-induced glucose uptake. Confluence 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.