NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Abstract

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 kB (NFkB). 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 NGTand 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 NFkB, as the NFkB 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.

Insulin therapy and fetoplacental vascular function in gestational diabetes mellitus

“…Normal fetoplacental vascular remodelling (Haas, 2014) and function Pardo et al 2013;Guzmán-Gutiérrez et al 2014) are required for normal fetal growth and development. Thus, alterations in placental structure and function have deleterious consequences for fetal development and growth as well as the health of the mother (König et al 2014;Lappas, 2014).…”

“…Thus, alterations in placental structure and function have deleterious consequences for fetal development and growth as well as the health of the mother (König et al . ; Lappas, ).…”

Gestational diabetes: An overview with attention for developing countries

“…IL-6, TNF-α, adipocyte fatty acid-binding protein (AFABP)] (Abell et al 2015). In Table 1, the main agents, involved in the GDM physiopathology, are reported (Qiu et al 2004;Lewandowski et al 2007;Mordwinkin et al 2013;Lappas 2014;Abell et al 2015;Iyidir et al 2015;.…”

Understanding the regulation of pattern recognition receptors in inflammatory diseases – a ‘Nod’ in the right direction

“…Finally, diet‐induced adipocyte inflammation, referred to as metabolic disease, can manifest as either metabolic syndrome or gestational diabetes mellitus. Enhanced NOD1 expression has been recorded in these diet‐induced conditions, supporting a role for NOD1 in ‘metainflammation’ . To conclude, current knowledge has identified a strong link between NOD1/NOD2 and IBD development.…”