High dietary salt intake activates inflammatory cascades via Th17 immune cells: impact on health and diseases.

The incidence of immune-mediated inflammatory diseases (IMIDs) is on the rise. A high salt content in the diet was found to play a crucial role in mediating IMIDs. It was demonstrated that increased salt concentration favors the differentiation of CD4+ cells to pathogenic Th17 cells, which predispose to several inflammatory diseases by modulating the immunological milieu. In auto-immune diseases increased salt concentration causes stable induction of Th17 cells. In cancer, increased salt concentration triggers chronic inflammation and increases vascular endothelial growth factor levels. Salt-mediated proliferation of Th17 cells has been found to reduce nitric oxide production in the endothelial cells, leading to hypertension. Increased salt concentration was found to alter the intestinal flora, which favors local inflammation. This review attempts to explain the role of high salt concentration and its molecular pathways in causing IMIDs.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism.

INTRODUCTION: Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. MATERIALS AND METHODS: Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. RESULTS: Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. CONCLUSION: Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

Decreased maternal serum adiponectin and increased insulin-like growth factor-1 levels along with increased placental glucose transporter-1 expression in gestational diabetes mellitus: Possible role in fetal overgrowth.

INTRODUCTION: The placental glucose transporter - 1 (GLUT-1) is involved in the transplacental glucose transport to the fetus. GLUT-1 expressions are increased in diabetic pregnancies and associated with altered fetal growth. However, the factors regulating the GLUT-1 expressions are largely unknown. We hypothesised that maternal adipokines and insulin-like growth factor-1 (IGF1) modulate the placental expressions of GLUT-1 through the activation of insulin/IGF-1 signalling which may contribute to a fetal overgrowth in GDM. METHODS: Maternal blood, cord blood and placental samples were collected from GDM and control pregnant women (CPW). The biochemical parameters, IGF1, adipokines, and high sensitive C- reactive protein were measured. We analysed the placental expressions of GLUT-1 and proteins related to insulin/IGF-1 signalling - insulin receptor -ß, insulin receptor substrate - 1, phosphatidylinositol-3-kinase p110α, phospho Akt-1, phospho extracellular signal-regulated kinase 1/2, and nuclear factor-κB p65 in GDM and CPW. RESULTS: Increased maternal IGF-1 and decreased adiponectin levels were found in the GDM women. Maternal IGF-1 levels were positively correlated, whereas adiponectin levels were negatively correlated with the birth weight of GDM newborns. Increased phosphorylation of Akt and ERK 1/2 was found in the placenta of GDM women. Placental expressions of GLUT-1 were significantly higher in the GDM women and positively correlated to the maternal IGF-1 levels in the GDM group. DISCUSSION: Decreased maternal adiponectin and increased IGF-1 levels might have caused increased GLUT-1 expression via the increased activation of insulin/IGF-1 signalling in the placenta of GDM women which might have influenced the fetal growth.

Increased placental expressions of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress?

OBJECTIVE: Gestational diabetes mellitus is associated with increased oxidative stress. Oxidative stress may contribute to the risk for pregnancy pathologies associated with gestational diabetes mellitus. In this study we investigated the expression of placental nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant enzymes of gestational diabetes mellitus and healthy pregnant women and correlated them with the maternal and cord plasma as well as placental tissue oxidative stress parameters. STUDY DESIGN: A cross sectional study was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty gestational diabetes mellitus patients in the gestational age of 32 ± 4weeks were recruited. Maternal plasma, cord plasma and placental oxidative stress parameters were measured. Placental expression of Nrf2, phospho Nrf2, catalase and superoxide dismutase 1(SOD1) were analyzed by western blotting and immunohistochemistry. RESULTS: Placental expression of Nrf2, catalase and SOD1 were found to be significantly higher in gestational diabetes mellitus. The maternal plasma, cord plasma and placental tissue oxidative stress parameters, total antioxidant status (TAS) levels were significantly lower; whereas MDA (malondialdehyde) and MDA/TAS levels were significantly higher in gestational diabetes mellitus. Placental Nrf2 expression correlated positively with the placental catalase expression and negatively with placental TAS levels in both groups. CONCLUSION: Maternal, fetal and placental oxidative stress was observed in gestational diabetes mellitus. The gestational diabetic placenta had an increased Nrf2 protein expression. The activated placental Nrf2/ antioxidant response element (ARE) pathway might have led to an increased expression of antioxidant enzymes SOD1 and catalase. This may be viewed as a protective mechanism in placenta from the further onslaught of oxidative stress.

Adipokine levels and their association with insulin resistance and fetal outcomes among the newborns of Indian gestational diabetic mothers.

OBJECTIVES: To investigate the cord blood levels of adipokine and to assess their association with the fetal insulin resistance and fetal outcomes in newborns of gestational diabetic women (GDM). Methods: This cross-sectional study was performed in 40 GDM women and 40 healthy pregnant women (HPW) in the Department of Obstetrics and Gynecology at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) hospital in Puducherry, India, during the period from May 2016 to December 2017. Cord blood samples were collected at delivery from GDM and HPW groups. Cord plasma biochemical parameters such as insulin, C-peptide, adiponectin, leptin, resistin, and visfatin concentrations were measured. Leptin/adiponectin ratio (L/A), homeostasis model assessment of insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-%S) and beta cell function (HOMA2-%B) were calculated. The pregnancy outcomes such as birth weight (BW), Ponderal index and Apgar scores of the baby were measured. Results: The BW and Ponderal index of the baby were found to be significantly higher in GDM newborns compared to HPW newborns. Cord plasma insulin, C-peptide, HOMA2 -IR, visfatin, leptin, and L/A ratio were significantly higher whereas adiponectin level was lower in GDM compared to HPW. A significant positive correlation was observed between L/A ratio and fetal HOMA2-IR. Conclusion: Altered adipokine levels with increased L/A ratio was observed among the new-borns of Indian gestational diabetic mothers. There was an association between increased L/A ratio, insulin resistance and increased Ponderal index among the new-borns.

Metabolomic Analysis and Antioxidant Effect of Amla (Emblica officinalis) Extract in Preventing Oxidative Stress-Induced Red Cell Damage and Plasma Protein Alterations: An In Vitro Study.

Amla (Emblica officinalis) has antidiabetic, hypolipidemic, anti-inflammatory, and antioxidant properties, but its effect on free radical induced red cell damage and membrane and plasma protein alterations has not been adequately addressed. The aim of the present study was to evaluate the antioxidant property of amla against oxidative stress-induced red cell damage and plasma protein alterations. Red blood cells (RBCs) were preincubated with different concentrations of amla extract (50, 100, 150, and 200 µg/mL) and then treated with physiological (5 mM) and pathological (50 mM) concentrations of glucose for 24 h. In another in vitro study the plasma was pretreated with different concentrations of amla extract and then incubated with 2, 2'-Azo-Bis (2-methylpropionamidine) dihydrochloride (AAPH) for 2 h. After the incubation RBC-malondialdehyde (MDA), RBC-reduced glutathione (GSH), RBC indices, RBC morphometric study, plasma MDA, protein carbonylation, total protein, and albumin were estimated. The antioxidant property of amla was assessed by DPPH assay. RBC-MDA levels were significantly decreased and RBC-GSH levels were significantly increased with higher concentration of amla extract (150 and 200 µg/mL). Red cell count and its indices were improved with the increasing concentration of amla. In addition, at higher concentration, amla restored the RBC membrane integrity. The plasma in vitro study also showed that amla improved the plasma MDA, protein carbonylation, total protein, and albumin levels. Amla extract effectively protected the RBCs and plasma proteins from the reactive oxygen species induced oxidative damage. Liquid chromatography-mass spectrometry (LC-MS) analysis of the extract revealed the presence of gallic acid, quinic acid, and quercetin as the major constituents in addition to the other flavonoids.

Role of omentin 1 and IL-6 in type 2 diabetes mellitus patients with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is one of the major chronic vascular complication of T2DM and leading cause of end-stage renal disease. Inflammation is one of the proposed pathway which explains microvascular complications in T2DM but exact mechanism is still unclear. Omentin-1 is an anti-inflammatory adipokine which promotes insulin signaling. IL-6 is a multifunctional cytokine having role in immune and inflammatory responses. The present study was conducted to elucidate the role of omentin-1 and IL-6 in the pathogenesis of DN and its association with insulin resistance. We aimed to assess and compare the serum levels of omentin-1 and IL-6 in T2DM patients with and without DN. MATERIALS & METHODS: Our study comprised of 2 groups of 41 each. Group A (controls) included T2DM without nephropathy patients and group B (cases) included T2DM nephropathy patients. Parameters studied were serum omentin-1, insulin, IL-6, fasting blood glucose, urea, creatinine, lipid profile, HOMA-IR, eGFR and BMI. RESULTS & CONCLUSION: Omentin-1 (p=0.03) was significantly decreased; concomitantly, significant increase in levels of insulin (p=0.004), IL-6 (p=0.023) and HOMA-IR (p=0.0004) were found in cases compared to controls. Bivariate analysis showed eGFR correlating positively with omentin-1 and negatively with insulin in the study population. Our study results, based on serum omentin-1 and IL-6 data suggest important role played by inflammatory mechanism and insulin resistance in the pathogenesis of diabetic nephropathy in type 2 diabetes mellitus patients.

Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity).

Obesity emerged as the major risk factor for metabolic syndrome. Postmenopausal women are more prone to develop obesity than premenopausal women. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedy. We investigated the molecular basis of the effect of soy isoflavones (SIFs) on hypertriglyceridemia and hepatic steatosis in an animal model of postmenopausal obesity. Ovariectomized (OVX) and sham-operated Wistar rats were fed with high-fat diet (HFD) and normal diet for 8 weeks with and without SIF extract (150mg/kg body weight/day). Both OVX and HFD per se and when combined caused hypertriglyceridemia, hypercholesterolemia and atherogenic lipid profile. Proteomic studies revealed that both OVX and HFD caused overexpression of hepatic lipogenic proteins, such as LXR, SREBP1, PPARγ, ACC and FAS, in association with reduced expression of lipolytic proteins, such as FXR, PPARα, insig2 and SHP. Histological analysis showed fat accumulation and morphological abnormalities in the liver of OVX and HFD rats. All these metabolic derangements were further augmented when OVX was followed by HFD. In conclusion, these findings suggest that there was a synergism in the development of deranged lipid metabolism with the coexistence of postmenopausal state and the intake of fat-rich diet. SIF extract markedly alleviated the derangement of lipid metabolism suggesting the use of this natural phytoestrogen as a strategy for relieving dyslipidemia and hepatic steatosis associated with the postmenopausal women.