Nucleotide-binding Oligomerization Domain-1 Ligand Induces Inflammation and Attenuates Glucose Uptake in Human Adipocytes

Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 （NOD1） on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes. Methods Adipose tissues were obtained from patients undergoing liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. A specific ligand for NOD1, was administered to human adipocytes in culture. Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay, respectively. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[ 3 H] glucose uptake assay. Furthermore, chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA （siRNA） targeting NOD1 upon stimulation of NOD1 ligand were analyzed. Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6, and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand （all P〈0.01）. Insulin-induced glucose uptake was decreased upon the activation of NOD1 （P〈0.05）. NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1, IL-6, and IL-8 release and increased insulin-induced glucose uptake （all P〈0.05）. Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.