2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

Abstract

Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (nZ6 patients per group). Western blotting was used for confirmation of six of the spot differences (nZ6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (R1.4-fold, P!0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM.

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

“…In addition, NOD1 activation provokes adipose tissue inflammation in vivo (Schertzer et al 2011). Collectively, these results indicate that NOD1 activation may facilitate the infiltration of leukocytes into adipose tissue, leading to adipose inflammation, a key feature of GDM pregnancies (Lappas 2013a, Oliva et al 2013. Moreover, NOD1-mediated release of pro-inflammatory cytokines from adipose tissue may directly contribute to the insulin resistance that is evident in pregnancies complicated by GDM (Catalano et al 2002, Colomiere et al 2010.…”

“…There is now some evidence that metabolic endotoxemia originating from the diet or the environment disrupts the balance between the immune and the metabolic systems (Cani et al 2007) which may lead to GDM. Thus, it is possible that this increase in bacteria may activate NOD1, leading to the increased inflammation and insulin resistance observed in women with GDM (Garvey et al 1993, Colomiere et al 2010, Lappas 2013a, Oliva et al 2013. Indeed, it has recently been shown that dietinduced modification of the gut flora with probiotics can ameliorate the insulin resistance and glucose homoeostasis of pregnant women (Laitinen et al 2009).…”

Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus

“…Up to now, no comprehensive proteomic analyses of plasma related to GDM have been reported. Only a few proteomic analyses of placental, omental adipose tissue related to GDM have been reported [9,10]. However, comprehensive analysis of the plasma is a challenging task because of its extraordinary complexity and high dynamic range in concentration [11].…”

Proteomic-driven biomarker discovery in gestational diabetes mellitus: A review

“…Several studies have reported abnormal expression of different proteins involved in glucose and lipid metabolism [23], inflammation [24] and oxidative stress [25] in GDM and thus, intricate…”