Obesity alone or with type 2 diabetes is associated with tissue specific alterations in DNA methylation and gene expression of PPARGC1A and IGF2

Objective. We investigated the expression levels of both FOSL2 mRNA and protein as well as evaluating DNA methylation in the blood of type 2 diabetes mellitus (T2DM) Uyghur patients from Xinjiang. This study also evaluated whether FOSL2 gene expression had demonstrated any associations with clinical and biochemical indicators of T2DM. Methods. One hundred Uyghur subjects where divided into two groups, T2DM and nonimpaired glucose tolerance (NGT) groups. DNA methylation of FOSL2 was also analyzed by MassARRAY Spectrometry and methylation data of individual units were generated by the EpiTyper v1.0.5 software. The expression levels of FOS-like antigen 2 (FOSL2) and the protein expression levels were analyzed. Results. Significant differences were observed in mRNA and protein levels when compared with the NGT group, while methylation rates of eight CpG units within the FOSL2 gene were higher in the T2DM group. Methylation of CpG sites was found to inversely correlate with expression of other markers. Conclusions. Results show that a correlation between mRNA, protein, and DNA methylation of FOSL2 gene exists among T2DM patients from Uyghur. FOSL2 protein and mRNA were downregulated and the DNA became hypermethylated, all of which may be involved in T2DM pathogenesis in this population.

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Decreased expression of genes involved in oxidative phosphorylation in human pancreatic islets from patients with type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje-11-0282 ◽

2011 ◽

Vol 165 (4) ◽

pp. 589-595 ◽

Cited By ~ 42

Author(s):

Anders H Olsson ◽

Beatrice T Yang ◽

Elin Hall ◽

Jalal Taneera ◽

Albert Salehi ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Insulin Secretion ◽

Oxidative Phosphorylation ◽

Pancreatic Islets ◽

Human Pancreatic Islets ◽

Qrt Pcr ◽

Glucose Stimulated Insulin Secretion

ObjectiveGene expression alterations, especially in target tissues of insulin, have been associated with type 2 diabetes (T2D). In this study, we examined if genes involved in oxidative phosphorylation (OXPHOS) show differential gene expression and DNA methylation in pancreatic islets from patients with T2D compared with non-diabetic donors.Design and methodsGene expression was analyzed in human pancreatic islets from 55 non-diabetic donors and nine T2D donors using microarray.ResultsWhile the expected number of OXPHOS genes with reduced gene expression is 7.21, we identified 21 downregulated OXPHOS genes in pancreatic islets from patients with T2D using microarray analysis. This gives a ratio of observed over expected OXPHOS genes of 26.37 by aχ2-test withP=2.81×10−7. The microarray data was validated by qRT-PCR for four selected OXPHOS genes:NDUFA5, NDUFA10, COX11, andATP6V1H. All four OXPHOS genes were significantly downregulated in islets from patients with T2D compared with non-diabetic donors using qRT-PCR (P≤0.01). Furthermore, HbAlc levels correlated negatively with gene expression ofNDUFA5, COX11, andATP6V1H(P<0.05). Gene expression ofNDUFA5, NDUFA10, COX11, andATP6V1Hcorrelated positively with glucose-stimulated insulin secretion (P<0.03). Finally, DNA methylation was analyzed upstream of the transcription start forNDUFA5, COX11, andATP6V1H. However, none of the analyzed CpG sites in the three genes showed differences in DNA methylation in islets from donors with T2D compared with non-diabetic donors.ConclusionPancreatic islets from patients with T2D show decreased expression of a set of OXPHOS genes, which may lead to impaired insulin secretion.

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The chemerin production changes in obese patients with different carbohydrate metabolism state

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20176306582 ◽

2017 ◽

Vol 63 (6) ◽

pp. 582-590 ◽

Cited By ~ 1

Author(s):

M.A. Vasilenko ◽

E.V. Kirienkova ◽

D.A. Skuratovskaya ◽

P.A. Zatolokin ◽

N.I. Mironyuk ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Mrna Expression ◽

Carbohydrate Metabolism ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Obese Patients ◽

Tissue Specific

Chemerin is a mediator of adipose tissue involved in the regulation of many processes, including lipogenesis, and inflammatory response. The role of chemerin in the development of insulin resistance has been insufficiently studied and needs detailed understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with a diagnosis of obesity; 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors who did not have obesity. For comparison of the results of a study to determine the levels of tissue-specific mRNA expression of the genes IL-6, TNF-a, RARRES2, (encoding IL-6, TNF-a and chemerin) in adipose tissue introduced a control group 2 – 30 patients without obesity. Study on the relative level of mRNA expression of the genes IL-6, TNF-a and RARRES2 (encoding IL-6, TNF-a and chemerin) was carried out using real time PCR. Concentrations of IL-6, TNF-a, and chemerin were measured in serum/plasma using an enzyme-linked immunosorbent assay (ELISA). We found significant differences in the plasma level of chemerin and tissue-specific features of RARRES2 gene expression in obese patients, depending on the degree of obesity and the state of carbohydrate metabolism. Multidirectional associations of RARRES2 gene expression with TNF-a and IL-6 genes in adipose tissues of different localization are shown: in obese patients (BMI £40 kg/m2) without type 2 diabetes – negative, and type 2 diabetes – positive. Identified relationship chemerin plasma content and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, proinflammatory molecules indicate chemerin involved in metabolic and immune processes in obesity.

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Kruppel-Like Transcription Factor-4 Gene Expression and DNA Methylation Status in Type 2 Diabetes and Diabetic Nephropathy Patients

Archives of Medical Research ◽

10.1016/j.arcmed.2019.05.012 ◽

2019 ◽

Vol 50 (3) ◽

pp. 91-97

Author(s):

Zeynep Mine Coskun ◽

Melike Ersoz ◽

Mine Adas ◽

Veysel Sabri Hancer ◽

Serife Nur Boysan ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Transcription Factor ◽

Diabetic Nephropathy ◽

Methylation Status ◽

Transcription Factor 4

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Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: results from the Korea Epigenome Study (KES)

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001338 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001338

Author(s):

In-Uk Koh ◽

Nak-Hyeon Choi ◽

Kibaick Lee ◽

Ho-Yeong Yu ◽

Jun Ho Yun ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Childhood Obesity ◽

Rna Sequencing ◽

Phase Iii ◽

Health Concern ◽

Fat Tissue ◽

Increased Risk

IntroductionObesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.Research design and methodsWe performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).ResultsSeven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.ConclusionsOur finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.

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