Nucleotide-binding oligomerization domain-1 ligand induces inflammation and attenuates glucose uptake in human adipocytes / 中国医学科学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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-[³H] 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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.</p>