Serum glypican 4 level in obese children and its relation to degree of obesity

Leelalertlauw, Chutima; Korwutthikulrangsri, Manassawee; Mahachoklertwattana, Pat; Chanprasertyothin, Suwannee; Khlairit, Patcharin; Pongratanakul, Sarunyu; Poomthavorn, Preamrudee

doi:10.1111/cen.13435

Cited by 19 publications

(21 citation statements)

References 28 publications

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“…In addition, the metabolic effect of high glucose and high osmotic pressure of GDM patients may contribute to the increased proteoglycan perlecan expression in diabetic placentas [22]. Leelalertlauw et al [23] found that serum glypican 4 levels were increased with increasing degrees of obesity. Furthermore, Ussar et al [24] demonstrated that circulating glypican-4 levels correlate with BMI and insulin sensitivity in humans.…”

Section: Resultsmentioning

confidence: 99%

Integrated miRNA-mRNA Expression Profile Analysis Reveals a Role of miR-146a-3p/TRAF6 in Plasma from Gestational Diabetes Mellitus Patients

Chen

Yan

2020

Preprint

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BACKGROUND: By utilizing an integrative strategy, we screened noninvasive molecular markers for the early detection of GDM and constructed miRNA-mRNA regulatory networks associated with GDM.METHODS: A total of 3 microarray datasets (GSE98043, GSE19649 and GSE92772) of plasma samples comparing GDM pregnant women and healthy control pregnant women were downloaded from the GEO database. The GEO2R online platform was used to identify the differentially expressed genes (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs). The target genes of DEmiRNAs were identified using two independent and complementary types of information: computational target predictions and expression relationships. KEGG pathway annotation was performed for target genes and DEmiRNAs. An interaction network was constructed to identify hub genes of GDM. Another dataset (GSE92772) was used to externally verify the predictive ability of the hub genes. Gene set enrichment analysis (GSEA) was performed to explore the biological function of hub genes.RESULTS: A total of 264 DEmiRNAs and 1217 DEmRNAs were identified by comparing the microarray data of serum samples of GDM patients and healthy pregnant women. Hsa-miR-146a-3p ranked first because of its lowest P value and was selected for further analysis. A total of 47 target genes, including TRAF6, were shared between the computational target predictions and DEmRNAs and were identified as target genes of hsa-miR-146a-3p. Enrichment analysis indicated that GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. In addition, the glypican pathway was also one of the pathways regulated by hsa-miR-146a-3p. The interaction network analysis of DEmRNAs identified TRAF6, CASP8, PTPN6, and CHD3 as hub genes involved in the pathophysiological process of GDM. Next, these 4 hub genes were selected for independent external validation using the GSE19649 dataset. The expression of TRAF6, CASP8 and CHD3 in 8 pairs of GDM blood samples was confirmed to be higher than that in healthy pregnant women blood samples. However, the expression of PTPN6 in the blood samples of GDM patients was similar to that of healthy pregnant women blood samples. The AUC for predicting GDM was 0.813, 0.828, 0.813, and 0.703 for CHD3, PTPN6, and CASP8, respectively. GSEA showed that 9 hallmark gene sets of metabolism processes were enriched in TRAF6 function.CONCLUSIONS: Three hub genes, TRAF6, CASP8, and CHD3, were identified and independently externally validated as potential GDM noninvasive serum markers. Enrichment analysis indicated that GDM-related miRNAs were mainly enriched in the glypican pathway, proteoglycan syndecan-mediated signaling events, and syndecan-1-mediated signaling events. In addition, integrated miRNA-mRNA expression profile analysis showed that miR-146a-3p/TRAF6 might play a central role in the pathogenesis of gestational diabetes mellitus by involving the above pathways.

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Section: Resultsmentioning

confidence: 99%

Integrated miRNA-mRNA Expression Profile Analysis Reveals a Role of miR-146a-3p/TRAF6 in Plasma from Gestational Diabetes Mellitus Patients

Chen

Yan

2020

Preprint

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“…In their study, Ussar et al found that glypican-4 levels correlated positively with BMI and insulin resistance, but did not find any correlation with fasting blood glucose and total cholesterol levels (3). Leelalertlauw et al reported a positive correlation with serum glypican-4 levels and HbA1c, total cholesterol, AST and ALT levels (15). Nevertheless, they did not explore any correlation between serum glypican-4 levels and insulin sensitivity and β-cell function indicators.…”

Section: Discussionmentioning

confidence: 96%

“…Our study was the first to examine the glypican-4 levels in the adolescent group aged 10 -16 years. In a study conducted by Leelalertlauw et al, in a group of children aged 8 -18 years, they found that serum glypican-4 levels increased as the obesity degree increased (15). Li et al showed that circulating glypican-4 levels in-creased in prediabetic adults and decreased in patients with type 2 diabetes mellitus (16).…”

Section: Discussionmentioning

confidence: 98%

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Increased Glypican-4 Levels Are Associated with Obesity in Adolescents

Dağ

Dikker

2019

Iran J Pediatr

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Background: Glypican-4 is an adipose tissue-originated cytokine which enhances insulin signaling through direct interaction with the insulin receptors. Objectives: The aim of this study was to analyze the relationship between obesity and serum glipican-4 levels in adolescents. Methods:Our study was carried out on 80 volunteer adolescents, 49 were obese patients and 31 were healthy normal weight control cases. The adolescents with a body mass index (BMI) of 95% percentile and over were defined as obese in terms of age and sex. The Enzyme-Linked Immuno Sorbent Assay kit was utilized for the assessment of Glypican-4 in serum. Laboratory assays (glypican-4, glucose, urea, creatinine, AST, ALT, total cholesterol, triglyceride, HbA1c, insulin, HOMA-IR), age, sex and BMI were compared amidst the groups. Correlations between glypican-4 levels and laboratory factors were analyzed in the obese adolescent group. Results:The average age of the research participants was 13.2 ± 1.8 years. The mean BMI was 27.1 ± 5.1 kg/m 2 . Of the 49 obese adolescents, 41 were insulin resistant, and 8 did not have insulin resistance. The levels of glypican-4, BMI, AST, ALT, HbA1c, triglyceride, HOMA-IR and insulin were notably higher in the obese group than the control group (P < 0.05). In obese group, no statistically remarkable relationship was found between glypican-4 levels and other parameters (P > 0.05). Conclusions:We found high serum glypican-4 levels in obese adolescents. We suggest that glypican-4 levels may be increased in order to reduce insulin resistance in obese adolescents.

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“…It was previously shown that both membrane-bound and soluble glypican4 are able to regulate insulin signaling due to direct interaction with the insulin receptor [4]. Furthermore, glypican4 serum levels are associated with obesity and insulin resistance in adult subjects [4,[7][8][9][10][11][12]. Glypican4 serum levels were shown to be increased in patients with obesity compared to normal weight controls.…”

Section: Introductionmentioning

confidence: 99%

How Reliable are Commercially Available Glypican4 ELISA Kits?

Buhl

Garten

Kratzsch

et al. 2020

Exp Clin Endocrinol Diabetes

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Objective Glypican4 is an interesting new adipokine, which seems to play an important role in developmental processes and is potentially associated with metabolic changes in obesity and type 2 diabetes mellitus. Currently, only a few studies examined glypican4 in human blood, mainly in adults. Design, Patients and Measurements The aim of our study was to investigate glypican4 serum levels in lean, overweight, and obese children and adolescents, to unravel a possible association between glypican4 serum levels and parameters of obesity and insulin resistance. In order to determine a suitable method for investigating glypican4 serum levels, we validated two commercially available human glypican4 ELISA kits, using serum and plasma samples of an obese, insulin-resistant patient, and a healthy control subject, a human recombinant glypican4 protein fragment and glypican4-overexpressing cell lysate. Results Using ELISA kit #1 we were not able to detect values above background level, apart from standard curve values. ELISA kit #2 initially seemed suitable to measure glypican4, but further validation experiments showed non-linearity of serial dilutions, no recognition of a human recombinant glypican4 protein fragment and non-linearity in the recovery of glypican4-overexpressing cell lysate. In addition, there was a considerable decrease (approx. 68%) of measured values between two experiments, performed at different time points with aliquots of the same serum sample. Contrary to that, further experiments found sample stability not to be compromised. Conclusions Extensive evaluation of the performance of two commercially available ELISA kits led to the conclusion that none of them is applicable for the measurement of glypican4 in human blood samples.

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Serum glypican 4 level in obese children and its relation to degree of obesity

Abstract: Serum Gpc4 levels were increased with increasing degrees of obesity. There were no differences in serum Gpc4 levels among glucose metabolism categories.

Cited by 19 publications

References 28 publications

Integrated miRNA-mRNA Expression Profile Analysis Reveals a Role of miR-146a-3p/TRAF6 in Plasma from Gestational Diabetes Mellitus Patients

Integrated miRNA-mRNA Expression Profile Analysis Reveals a Role of miR-146a-3p/TRAF6 in Plasma from Gestational Diabetes Mellitus Patients

Increased Glypican-4 Levels Are Associated with Obesity in Adolescents

How Reliable are Commercially Available Glypican4 ELISA Kits?

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