title: Saturated fatty acid induces insulin resistance partially through nucleotide-binding oligomerization domain 1 signaling pathway in adipocytes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Yi-jun
authors.initials: YJ
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Yin-si
authors.initials: YS
authors.lastname: Tang
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Yu-ling
authors.initials: YL
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology and Metabolism, Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005227:Fatty Acids / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D005227:Fatty Acids; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4