The role of immune receptor NOD1 in insulin resistance of human adipocytes

Abstract

Objective To investigate the role of nucleotide-binding oligomerization domain-containing protein 1 （NOD1） in inducing insulin resistance in differentiated human adipocytes. Methods Human preadipocytes obtained via liposuction were induced to differentiate into mature adipocytes. iE-DAP, a specific ligand for NOD1, was administered to human adipocytes in culture. NF-κB transcriptional activity and proinflammatory cytokines production were determined by luciferase assay and enzyme-linked immunosorbent assay. Glucose uptake in adipocytes was measured by 2-deoxy-D-[3H] glucose uptake （P〈0.05）. The expression of phosphatidylinositol-3-kinase p85 （PI-3K p85）, insulin receptor substrate-1（IRS-1） and Akt phosphorylations were detected by Western blotting. Results NF-κB transcriptional activity and cytokines such as interleukin （IL）-6, IL-8, and monocyte chemotactic protein 1 secretion were markedly increased after stimulation with iE-DAP （P〈0.05 or P〈0.01）. Insulin-induced glucose uptake was decreased with the activation of NOD1 in a dose- and time-dependent fashion. NOD1 activation weakened insulin signal transduction as being revealed by increasing IRS-1 Ser307 phosphorylation, reducing protein expression of PI-3K p85, and attenuating insulin-induced phosphorylation of Akt on Ser473and Thr308in human adipocytes. Conclusion These results indicate that NOD1 activation induces inflammatory response and insulin resistance via IRS-1/PI3-K/Akt signaling pathway in human adipocytes. Key words: Nucleotide-binding oligomerization domain-containing protein 1 ; Insulin resistance; Human adipocytes ; γ-D-Glu-meso-diaminopimelic acid ; Inflammation