NOD1 expression is increased in the adipose tissue of women with gestational diabetes.
Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies, complicated by gestational diabetes mellitus (GDM). The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor κB (NFκB). The aim of this study was to determine whether levels of NOD1 and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous adipose tissues obtained from women with GDM when compared with those from women with normal glucose tolerance (NGT). In both omental and subcutaneous adipose tissues from NGT and GDM women, the NOD1 ligand g-d-glutamyl-meso-diaminopimelic acid (iE-DAP) significantly induced the expression and secretion of the pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8; COX2 (PTGS2) gene expression and subsequent prostaglandin production; the expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion molecules ICAM1 and VCAM1. There was no effect of the NOD2 ligand muramyl dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP were mediated via NFκB, as the NFκB inhibitor BAY 11-7082 significantly attenuated iE-DAP-induced expression and secretion of pro-inflammatory cytokines, COX2 gene expression and subsequent prostaglandin production, MMP9 expression and secretion and ICAM1 and VCAM1 gene expression and secretion. In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.
ObstetricsNutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Level 4/163 Studley Road, Heidelberg, Victoria 3084, AustraliaMercy Perinatal Research CentreMercy Hospital for Women, Heidelberg, Victoria, AustraliaObstetricsNutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Level 4/163 Studley Road, Heidelberg, Victoria 3084, AustraliaMercy Perinatal Research CentreMercy Hospital for Women, Heidelberg, Victoria, Australia mlappas@unimelb.edu.au.
Martha
M
Lappas
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000096:biosynthesis*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C573420:ICAM1 protein, human; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020780:Matrix Metalloproteinase 9
NOD1; adipose tissue; gestational diabetes; inflammation; insulin resistance