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-[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.


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).


CONCLUSIONS
NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.
Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China. zhoudoctor@163.com
Zhou
Z
Yi-Jun
Li
L
Ai
Song
S
Yu-Ling
Li
L
Yan
Yan
Y
Hui
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D007333:Insulin Resistance; D008024:Ligands; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*
D016207:Cytokines; D008024:Ligands; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D005947:Glucose