scholarly journals Insulin resistance in obese adolescents affects the expression of genes associated with immune response

2019 ◽  
Vol 53 (2) ◽  
pp. 71-82 ◽  
Author(s):  
Dmytro O. Minchenko

AbstractObjective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.

2019 ◽  
Vol 53 (1) ◽  
pp. 34-45 ◽  
Author(s):  
Dmytro O. Minchenko ◽  
Dariia O. Tsymbal ◽  
Vadim V. Davydov ◽  
Oleksandr H. Minchenko

AbstractObjective. The development of obesity and its metabolic complications is associated with dys-regulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. The main goal of this work was to study the association between the expression of insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins and insulin resistance in obese adolescents for evaluation of possible contribution of these genes in development of insulin resistance.Methods. The expression of IGF1, IGF2, and IGFBPs mRNA was measured in blood of obese adolescents with normal insulin sensitivity and insulin resistance in comparison with the normal (control) individuals.Results. In the blood of obese adolescents with normal insulin sensitivity the expression of IGFBP4, IGFBP5 and HTRA1 genes was down-regulated, but IGFBP2 and IGFBP7 genes up-regulated as compared to control (normal) group. At the same time, no significant changes in IGF1 and IGF2 gene expressions in this group of obese adolescents were found. Insulin resistance in obese adolescents led to up-regulation of IGF2, IGFBP2, and IGFBP7 gene expressions as well as to down-regulation of the expression of IGF1, IGFBP5 and HTRA1 genes in the blood in comparison with the obese patients, which have normal insulin sensitivity. Furthermore, the level of IGFBP4 gene expression was similar in both groups of obese adolescents.Conclusions. Results of this investigation provide evidence that insulin resistance in obese adolescents is associated with gene specific changes in the expression of IGF1, IGF2, IGFBP2, IGFBP5, IGFBP7, and HTRA1 genes and these changes possibly contribute to the development of glucose intolerance and insulin resistance.


2021 ◽  
Vol 22 (4) ◽  
pp. 2061
Author(s):  
Przemysław Kołodziej ◽  
Marcin Nicoś ◽  
Paweł A. Krawczyk ◽  
Jacek Bogucki ◽  
Agnieszka Karczmarczyk ◽  
...  

There is an urgent need to seek new molecular biomarkers helpful in diagnosing and treating breast cancer. In this elaboration, we performed a molecular analysis of mutations and expression of genes within the PI3K/Akt/mTOR pathway in patients with ductal breast cancer of various malignancy levels. We recognized significant correlations between the expression levels of the studied genes. We also performed a bioinformatics analysis of the data available on the international database TCGA and compared them with our own research. Studies on mutations and expression of genes were conducted using High-Resolution Melt PCR (HRM-PCR), Allele-Specific-quantitative PCR (ASP-qPCR), Real-Time PCR molecular methods in a group of women with ductal breast cancer. Bioinformatics analysis was carried out using web source Ualcan and bc-GenExMiner. In the studied group of women, it was observed that the prevalence of mutations in the studied PIK3CA and AKT1 genes was 29.63%. It was stated that the average expression level of the PIK3CA, PIK3R1, PTEN genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the AKT1 and mTOR genes in the studied group was higher in comparison to the control group. It was also indicated that in the group of patients with mutations in the area of the PIK3CA and AKT1 genes, the PIK3CA gene expression level is statistically significantly lower than in the group without mutations. According to our knowledge, we demonstrate, for the first time, that there is a very strong positive correlation between the levels of AKT1 and mTOR gene expression in the case of patients with mutations and without mutations.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1704-1704
Author(s):  
Mónica del Rey ◽  
Kathleen O'Hagan ◽  
Margaret Dellett ◽  
Sara Aibar ◽  
Hilary A. A. Colyer ◽  
...  

Abstract Abstract 1704 Gene expression profiling studies have been performed in MDS to better characterize these diseases. However, the molecular pathogenesis of low-risk MDS is not yet fully understood. Furthermore, the transcriptional activity is dependent on many factors including epigenetic modifications. Therefore the integration of genome-wide epigenetic regulatory marks along with gene expression levels would provide additional information regarding the biological characteristics of low-risk MDS. A total of 83 low-risk MDS patients and 36 age-matched controls were included in the study. A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation and expression, while the whole series was used as a control group of expression data. Both the RNA and the DNA were isolated from BM mononucleate cells and hybridised with the Human Genome Expression Array (U133 Plus) from Affymetrix and MCAM Array from University Health Network (Canada), respectively. For analysis and interpretation of the hybridisation results, the R/Bioconductor program, DAVID bioinformatic resource, the web-delivered bioinformatics tool set Ingenuity Pathway Analysis and Metacore Analytical Suite were used. The results generated by expression and methylation microarrays were confirmed using Q- PCR and pyrosequencing, respectively. A total of 817 differentially methylated genes were identified as being present in low-risk MDS (p< 0.10); hyper-methylated genes (n=457) were more frequent than hypo-methylated genes (n=360). In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hyper-methylated genes were under-expressed in low-risk MDS cases. The most represented categories were regulation of apoptosis, gene expression, immune response and RNA process. BCL2, ETS1, IL27RA and DICER1, all of them hyper-methylated and down-expressed, were the most significant genes related to these functions. 1. Regarding apoptosis and BCL2, an over-expression of BCL2L11 and MYC were found in low-risk MDS. In contrast, BAX and CUX1 were under-expressed with respect to the control group. In addition, SYK gene was also hyper-methylated and under-expressed. 2. Promoter region analysis demonstrated that ETS1 transcription factor was involved in the regulation of 83 target genes included in the down-regulation signature of the low-risk MDS patients. The most significant functions of these target genes revealed that the cell-to-cell signaling and interaction pathway were prominently affected. In addition, apoptosis was identified as the function with the most number of down-regulated target genes. Therefore, the overall apoptosis pathway could be affected in low-risk MDS patients in two ways: methylation and decreased expression of BCL2 with the deregulation of related genes, as well as methylation and decreased expression of the ETS1 transcription factor with the deregulation of the apoptosis-related targets. 3. Regarding immune response, the study showed that besides IL27RA, another nine interleukins and interleukin receptors were under-expressed in the same cohort of patients: IL16, IL32, IL1RAP, IL2RB, IL6R, IL7R, IL10RA, IL10RB and IL13RA1. Three of them (IL16, IL1RAP and IL10RB) had direct genetic interactions with IL27RA. 4. Finally, the identification of DICER1 as a gene significantly altered by methylation and expression in low-risk MDS prompted us to measure the 183 miRNAs expression. A general down-regulation of miRNAs was observed in low-risk MDS cases respect to the control group (p=0.039). Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could play a central role in these diseases. Furthermore, we highlight candidate DNA methylation changes associated with low-risk MDS patients. Disclosures: No relevant conflicts of interest to declare.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Haijing Wang ◽  
Daoxin Liu ◽  
Pengfei Song ◽  
Feng Jiang ◽  
Xiangwen Chi ◽  
...  

Abstract Background The spleen is the largest secondary lymphoid organ and the main site where stress erythropoiesis occurs. It is known that hypoxia triggers the expansion of erythroid progenitors; however, its effects on splenic gene expression are still unclear. Here, we examined splenic global gene expression patterns by time-series RNA-seq after exposing mice to hypoxia for 0, 1, 3, 5, 7 and 13 days. Results Morphological analysis showed that on the 3rd day there was a significant increase in the spleen index and in the proliferation of erythroid progenitors. RNA-sequencing analysis revealed that the overall expression of genes decreased with increased hypoxic exposure. Compared with the control group, 1380, 3430, 4396, 3026, and 1636 genes were differentially expressed on days 1, 3, 5, 7 and 13, respectively. Clustering analysis of the intersection of differentially expressed genes pointed to 739 genes, 628 of which were upregulated, and GO analysis revealed a significant enrichment for cell proliferation. Enriched GO terms of downregulated genes were associated with immune cell activation. Expression of Gata1, Tal1 and Klf1 was significantly altered during stress erythropoiesis. Furthermore, expression of genes involved in the immune response was inhibited, and NK cells decreased. Conclusions The spleen of mice conquer hypoxia exposure in two ways. Stress erythropoiesis regulated by three transcription factors and genes in immune response were downregulated. These findings expand our knowledge of splenic transcriptional changes during hypoxia.


Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5972-5972
Author(s):  
Eva Klimčáková ◽  
Balbine Roussel ◽  
Adriana Márquez-Quiñones ◽  
Zuzana Kováčová ◽  
Michaela Kováčiková ◽  
...  

Context: It is not known whether biological differences reported between sc adipose tissue (SAT) and visceral adipose tissue (VAT) depots underlie the pathogenicity of visceral fat. Objective: We compared SAT and VAT gene expression according to obesity, visceral fat accumulation, insulin resistance, and presence of the metabolic syndrome. Design: Subjects were assigned into four groups (lean, overweight, obese, and obese with metabolic syndrome). Setting: Subjects were recruited at a university hospital. Patients: Thirty-two women were included. Main Outcome Measures: Anthropometric measurements, euglycemic-hyperinsulinemic clamps, blood analyses, and computed tomography scans were performed, and paired samples of SAT and VAT were obtained for DNA microarray-based gene expression profiling. Results: Considering the two fat depots together, 1125 genes were more and 1025 genes were less expressed in lean compared with metabolic syndrome subjects. Functional annotation clustering showed, from lean to metabolic syndrome subjects, progressive down-regulation of metabolic pathways including branched-chain amino acid, fatty acid, carbohydrate, and mitochondrial energy metabolism and up-regulation of immune response genes involved in toll-like receptor, TNF, nuclear factor-κB, and apoptosis pathways. Metabolism and immune response genes showed an opposite correlation with fat mass, fat distribution, or insulin resistance indices. These associations were similar in SAT and VAT, although about 1000 genes showed differential expression between SAT and VAT. Conclusions: The increase in adiposity and the worsening of metabolic status are associated with a coordinated down-regulation of metabolism-related and up-regulation of immune response-related gene expression. Molecular adaptations in SAT prove as discriminating as those in VAT.


2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Criado-Mesas ◽  
N. Abdelli ◽  
A. Noce ◽  
M. Farré ◽  
J. F. Pérez ◽  
...  

AbstractThere is a high interest on gut health in poultry with special focus on consequences of the intestinal diseases, such as coccidiosis and C. perfringens-induced necrotic enteritis (NE). We developed a custom gene expression panel, which could provide a snapshot of gene expression variation under challenging conditions. Ileum gene expression studies were performed through high throughput reverse transcription quantitative real-time polymerase chain reaction. A deep review on the bibliography was done and genes related to intestinal health were selected for barrier function, immune response, oxidation, digestive hormones, nutrient transport, and metabolism. The panel was firstly tested by using a nutritional/Clostridium perfringens model of intestinal barrier failure (induced using commercial reused litter and wheat-based diets without exogenous supplementation of enzymes) and the consistency of results was evaluated by another experiment under a coccidiosis challenge (orally gavaged with a commercial coccidiosis vaccine, 90× vaccine dose). Growth traits and intestinal morphological analysis were performed to check the gut barrier failure occurrence. Results of ileum gene expression showed a higher expression in genes involved in barrier function and nutrient transport in chickens raised in healthy conditions, while genes involved in immune response presented higher expression in C.perfringens-challenged birds. On the other hand, the Eimeria challenge also altered the expression of genes related to barrier function and metabolism, and increased the expression of genes related to immune response and oxidative stress. The panel developed in the current study gives us an overview of genes and pathways involved in broiler response to pathogen challenge. It also allows us to deep into the study of differences in gene expression pattern and magnitude of responses under either a coccidial vaccine or a NE.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1103
Author(s):  
Keyla Santos Guedes de Sá ◽  
Ednelza da Silva Graça Amoras ◽  
Simone Regina Souza da Silva Conde ◽  
Maria Alice Freitas Queiroz ◽  
Izaura Maria Vieira Cayres-Vallinoto ◽  
...  

An inefficient immune response against the hepatitis C virus (HCV), combined with viral evasion mechanisms, is responsible for the chronicity of infection. The need to evaluate the innate mechanisms of the immune response, such as TLR3 and IFN-λ3, and their relationship with the virus–host interaction is important for understanding the pathogenesis of chronic hepatitis C. The present study aimed to investigate the gene expressions of TRL3 and IFNL3 in liver tissue, seeking to evaluate whether these could be potential biomarkers of HCV infection. A total of 23 liver biopsy samples were collected from patients with chronic HCV, and 8 biopsies were collected from healthy control patients. RNA extraction, reverse transcription and qPCR were performed to quantify the relative gene expressions of TLR3 and IFNL3. Data on the viral load; AST, ALT, GGT and AFP levels; and the viral genotype were collected from the patients′ medical records. The intrahepatic expression of TLR3 (p = 0.0326) was higher in chronic HCV carriers than in the control group, and the expression of IFNL3 (p = 0.0037) was lower in chronic HCV carriers than in the healthy control group. The expression levels of TLR3 (p = 0.0030) and IFNL3 (p = 0.0036) were higher in the early stages of fibrosis and of necroinflammatory activity in the liver; in contrast, TLR3 and IFNL3 expressions were lower in the more advanced stages of fibrosis and inflammation. There was no correlation between the gene expression and the serum viral load. Regarding the initial METAVIR scale scores, liver transaminase levels were lower in patients with advanced fibrosis when correlated with TLR3 and IFNL3 gene expressions. The results suggest that in the early stages of the development of hepatic fibrosis, TLR3 and IFN-λ3 play important roles in the antiviral response and in the modulation of the tolerogenic liver environment because there is a decrease in the intrahepatic expressions of TLR3 and IFNL3 in the advanced stages of fibrosis, probably due to viral evasion mechanisms.


2018 ◽  
Vol 23 (2) ◽  
pp. 84
Author(s):  
Eunice Limantara ◽  
Felicia Kartawidjajaputra ◽  
Antonius Suwanto

Early detection of insulin resistance (IR) or non-alcoholic fatty liver disease (NAFLD) is crucial to preventing future risks of developing chronic diseases. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Liver Fat Score (LFS), and Fatty Liver Index (FLI) are generally employed to measure severity stages of IR and NAFLD. The study of gene expressions could explain the molecular mechanisms that occur early on in IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the gene expressions that could potentially be early markers of IR and NAFLD. All participants (n = 21) had normal blood glucose and were categorized as without hepatosteatosis (n = 10), at higher risk of hepatosteatosis (n = 6), and hepatosteatosis (n = 5). Gene expression analysis was performed using the 2-∆∆CT relative quantification method. There were significant differences in galnt2 (p < 0.002) and sirt1 (p < 0.010) expression between the first and the third tertiles of HOMA-IR; and in ptpn1 (p < 0.012) expression between the first and the second tertiles of LFS. In conclusion, the expressions of galnt2 and sirt1 could be used as early markers of IR, while the expression of ptpn1 could be employed as an early marker of NAFLD.


Author(s):  
I. Ilienko ◽  
◽  
D. Bazyka ◽  
N. Golyarnyk ◽  
L. Zvarych ◽  
...  

Objective. to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. Materials and methods. We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years (M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the control group: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1, IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined in peripheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The «gene-disease» association was determined on statistical models stratified separately for each disease and gene. Logistic regression was used to calculate the odds ratio. Results. Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression were found in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53, VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases an increase of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activation of the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes of angiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-up workers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantly upregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. Conclusions. Changes in the expression of genes, associated with the development of somatic pathology in the remote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2, IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A, SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF. Key words: gene expression, somatic pathology, radiation, Chornobyl.


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