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

2014 ◽  
Vol 222 (1) ◽  
pp. 99-112 ◽  
Author(s):  
Martha Lappas

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 moleculesICAM1andVCAM1. 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,COX2gene expression and subsequent prostaglandin production,MMP9expression and secretion andICAM1andVCAM1gene 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.

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Emad Yuzbashian ◽  
Golaleh Asghari ◽  
Maryam Aghayan ◽  
Mehdi Hedayati ◽  
Maryam Zarkesh ◽  
...  

Abstract Background Apelin, as an adipokine, plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. This study aimed to determine whether the quality and quantity of dietary carbohydrates were associated with apelin gene expression in subcutaneous and visceral adipose tissues. Methods In this cross-sectional study, 102 adults who underwent minor abdominal surgery were selected. Approximately 100 mg of subcutaneous and visceral adipose tissues were collected during the surgery to measure apelin gene expression. Anthropometric measurment, blood samples, and dietary intakes were collected before surgery. The dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) were determined. Results The average apelin concentration was 269.6 ± 98.5(pg/mL), and 16.3% of participants were insulin resistant. There was a correlation between insulin (p-value = 0.043), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)(p-value = 0.045) and apelin gene expression in visceral adipose tissue. There was a positive association of apelin gene expression with dietary GI and GL after adjustment for age, sex, and waist circumference in visceral and subcutaneous adipose tissues(p < 0.05). Apelin gene expression in visceral(p = 0.002) and subcutaneous(p = 0.003) adipose tissues was directly associated with foods with a higher GI. There was no association between total carbohydrate intake and apelin gene expression in both visceral and subcutaneous adipose tissues. Conclusions Dietary GI and GL, not total carbohydrate intake, were positively associated with apelin gene expression in both visceral and subcutaneous adipose tissues. Future studies are warranted to illustrate the chronic and acute effect of carbohydrate quality on apelin homeostasis.


2004 ◽  
Vol 286 (6) ◽  
pp. E941-E949 ◽  
Author(s):  
Jussi Sutinen ◽  
Katja Kannisto ◽  
Elena Korsheninnikova ◽  
Rachel M. Fisher ◽  
Ewa Ehrenborg ◽  
...  

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPARγ), and PPARγ coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARδ, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.


2020 ◽  
Author(s):  
Emad Yuzbashian ◽  
Maryam Zarkesh ◽  
Golaleh Asghari ◽  
Mehdi Hedayati ◽  
Parvin Mirmiran ◽  
...  

Abstract Background: The aim of the present study was to investigate the association of habitual intake of total fatty acids, saturated-, monounsaturated-, polyunsaturated fatty acids, n-3, n-6, and n-9 fatty acids with apelin gene expression in visceral and subcutaneous adipose tissue. Methods: We obtained visceral and subcutaneous adipose tissues from 179 participants (71 non-obese and 105 obese), who had undergone open abdominal surgery. Dietary intake information was gathered with a valid and reliable food frequency questionnaire. The mRNA expression of apelin gene was analyzed by Real-Time PCR. Results: Apelin gene expression was found to be more increased in subcutaneous and visceral adipose tissues in obese than in non-obese participants. Dietary intake of n-3 and polyunsaturated fatty acids was associated with apelin gene expression in subcutaneous and visceral adipose tissues among all categories of weight status after adjusting for total energy intake. Among obese individuals, visceral adipose tissue apelin mRNA levels were associated with total fat intake. Conclusion: Higher apelin gene expression in adipocytes had an association with habitual intake of total fat and n-3 fatty acids in obese and non-obese individuals, indicating a determinative role of quality and quantity of fatty acid intake in a regular diet in adipose tissue adipokine.


2010 ◽  
Vol 162 (3) ◽  
pp. 515-523 ◽  
Author(s):  
Karen Ruschke ◽  
Lauren Fishbein ◽  
Arne Dietrich ◽  
Nora Klöting ◽  
Anke Tönjes ◽  
...  

ObjectiveObesity and type 2 diabetes (T2D) are reaching epidemic proportions in Western societies, and they contribute to substantial morbidity and mortality. The peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) system plays an important role in the regulation of efficient energy utilization and oxidative phosphorylation, both of which are decreased in obesity and insulin resistance.Design and methodsWe measured the metabolic parameters and the expression of PPARγ and PGC-1α mRNA using quantitative real-time PCR in omental and subcutaneous (SC) adipose tissues in an observational study of 153 individuals as well as in SC fat and skeletal muscle in an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and T2D) before and after intensive physical training for 4 weeks.ResultsPPARγ and PGC-1α mRNA expression in both fat depots as well as in skeletal muscle is associated with markers of insulin resistance and cardiovascular risk. PGC-1α mRNA expression is significantly higher in SC fat than in omental fat, whereas PPARγ mRNA expression is not significantly different between these fat depots. Skeletal muscle and SC fat PPARγ and PGC-1α mRNA expression increased significantly in response to physical training.ConclusionsGene expression of PPARγ and PGC-1α in human adipose tissue is related to markers of insulin resistance and cardiovascular risk. Increased muscle and adipose tissue PPARγ and PGC-1α expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.


2012 ◽  
Vol 167 (5) ◽  
pp. 705-713 ◽  
Author(s):  
Tao Tao ◽  
Shengxian Li ◽  
Aimin Zhao ◽  
Yanyun Zhang ◽  
Wei Liu

Objective Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results The gene expression levels of CD11c along with TNF α and leptin in SAT remained significantly higher in PCOS women than in normal women (P<0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (P>0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFα (sTNFα) than did CD68 mRNA abundance. Lastly, increased sTNFα was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFα in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.


2021 ◽  
Author(s):  
Afsoon Daneshafrooz ◽  
Emad Yuzbashian ◽  
Maryam Zarkesh ◽  
Golaleh Asghari ◽  
Parvin Mirmiran ◽  
...  

Abstract Background Adipose tissue (AT) is known as a passive reservoir for energy storage and an active endocrine organ responsible for the synthesis of bioactive molecules called adipokines. Omentin is known as an anti-inflammatory adipokine that can modulate insulin sensitivity. In the present study, we aimed to investigate the relationship between omentin mRNA expression and glucose homeostasis of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in non-diabetic adults. Methods VAT and SAT adipose tissues were collected from 137 adults, aged ≥ 18 years, who were hospitalized for abdominal surgery. Preoperative venous blood samples were taken from the participants before surgery to measure fasting plasma glucose, insulin, and triglyceride. BMI, HOMA-IR, and HOMA-B were calculated. Insulin levels were measured with Mercodia kits using enzyme-linked immunosorbent assay (ELISA). In order to obtain omentin mRNA expression, real-time PCR was performed. Results Overall, 91 (51.7%) subjects were healthy (without insulin resistance (IR)), and 46 (26.1%) participants were with IR. Fold changes of VAT and SAT omentin expression in IR subjects were 2.32 and 1.30, respectively (P > 0.05). After controlling for age and BMI, linear regression analysis indicated a significant positive association of SAT omentin expression with insulin concentration (β = 0.048; 95% CI: 0.009, 0.088, P = 0.017) and HOMA-IR (β = 0.173; 95% CI: 0.023, 0.323, P = 0.014). Moreover, a negative association of SAT omentin expression with HOMA-B (β=-0.001; 95% CI: 0.002, -0.001, P < 0.001) was observed. Conclusion This study's finding confirms a direct association between IR with omentin mRNA levels in SAT. Besides, the indicator of insulin sensitivity had an inverse association with omentin gene expression in SAT. This aspect of research suggests that omentin secretion from SAT has a strong link with insulin regulation.


Author(s):  
Irving L M H Aye ◽  
Fredrick J Rosario ◽  
Anita Kramer ◽  
Oddrun Kristiansen ◽  
Trond M Michelsen ◽  
...  

Abstract Context Circulating adiponectin levels are decreased in pregnant women with obesity or gestational diabetes, and this is believed to contribute to the insulin resistance and increased risk of fetal overgrowth associated with these conditions. However, the molecular mechanisms regulating adiponectin secretion from maternal adipose tissues in pregnancy are poorly understood. Objective We tested the hypothesis that obesity in pregnancy is associated with adipose tissue insulin resistance and increased adiponectin ubiquitination and degradation, caused by inflammation and endoplasmic reticulum (ER) stress. Methods Visceral adipose tissues were collected from lean and obese pregnant humans and mice. Total and ubiquitinated adiponectin, and markers of inflammation, ER stress, and insulin resistance were examined in adipose tissues. The role of insulin, inflammation, and ER stress in mediating adiponectin ubiquitination and degradation was examined using 3T3L-1 adipocytes. Results Obesity in pregnancy is associated with adipose tissue inflammation, ER stress, insulin resistance, increased adiponectin ubiquitination, and decreased total abundance of adiponectin. Adiponectin ubiquitination was increased in visceral fat of obese pregnant women as compared to lean pregnant women. We further observed that insulin prevents, whereas ER stress and inflammation promote, adiponectin ubiquitination and degradation in differentiated 3T3-L1 adipocytes. Conclusion We have identified adiponectin ubiquitination as a key mechanism by which obesity diminishes adiponectin secretion in pregnancy. This information will help us better understand the mechanisms controlling maternal insulin resistance and fetal growth in pregnancy and may provide a foundation for the development of strategies aimed at improving adiponectin production in pregnant women with obesity or gestational diabetes.


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