Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes

Mirzaeicheshmeh, Elaheh; Zerrweck, Carlos; Centeno-Cruz, Federico; Baca-Peynado, Paulina; Martínez‐Hernández, Angélica; Garcia‐Ortíz, Humberto; Contreras-Cubas, Cecilia; Salas-Martínez, M; Saldaña-Álvarez, Yolanda; Mendoza-Caamal, Elvia; Barajas‐Olmos, Francisco; Orozco, Lorena

doi:10.1080/21623945.2021.1978157

Cited by 6 publications

(5 citation statements)

References 69 publications

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“…Multiple alterations were found in the human leukocyte antigen (HLA) region. Remarkably, similar findings were observed during adipogenesis in vitro from mesenchymal stem cells isolated from the same biopsies analyzed in the present study, suggesting that our observations are derived from the adipocytes and not from the infiltrating inflammatory cells whose numbers are increased in obesity [16]. In addition, a recent study compiling methylation data from adipose tissue found the most altered methylation at HLA in metabolically unhealthy patients with obesity [6].…”

Section: Discussionsupporting

confidence: 91%

“…However, the interplay between DNA methylation and gene expression is complex, because different genomic regions can exert a variety of influences on a given gene [9]. Some studies have addressed this issue, but studies that have paired DNA methylation and gene expression analyses in the context of T2D are scarce [10][11][12][13][14][15][16]. In this study, we aimed to extend our understanding of the pathogenesis of T2D in obesity by investigating DNA methylation differences between VAT samples from obese individuals with and without T2D.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity

et al. 2022

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Background Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone—epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity. Methods We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs], p value < 0.05) and gene expression (DEGs, p value <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested. Results We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (p values <0.05). Of these, 16, including ATP11A, LPL and EHD2 also showed a significant correlation with fasting glucose and HbA1c levels. Conclusions Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity

et al. 2022

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“…When we considered the hypomethylated regions, we found genes such as FN3K , which has been associated with HbA1clevels [ 57 ]. In addition, the RPH3AL and HOX genes are known to suffer DNA methylation alterations during adipogenesis in cells from obese patients with and without type II diabetes [ 60 ]. We also observed alterations in epigenetic modifiers such as HDAC4 , whose mutation impairs β-cell function and insulin secretion, leading to a non-autoimmune paediatric diabetes [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways

Alba-Linares

Pérez

Tejedor

et al. 2023

Cardiovasc Diabetol

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Background Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life. Methods We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics. Results We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations. Conclusions Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes.

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“…Among patients with T2D, the elevated expression of DNA damage‐inducible β (Gadd45β), in conjunction with TET1, stimulates the DNA demethylation of the PPARG coactivator 1 alpha (PPARGC1A) promoter, resulting in heightened gluconeogenesis and reduced glucose tolerance among patients 76 . DNAm alterations are evident across all three stages of adipogenesis in obese individuals, and these differentially methylated genes may play a role in the development of T2D primarily by impairing the function of mature adipocytes 77 …”

Section: Dnam In Obesity‐associated Diseasesmentioning

confidence: 99%

Epigenetic modifications in obesity‐associated diseases

Long,

Mao,

Liu

et al. 2024

MedComm

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The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity‐related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity‐associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity‐associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.

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Alterations of DNA methylation during adipogenesis differentiation of mesenchymal stem cells isolated from adipose tissue of patients with obesity is associated with type 2 diabetes

Cited by 6 publications

References 69 publications

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity

Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways

Epigenetic modifications in obesity‐associated diseases

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