Fat mass and obesity-associated (FTO) gene epigenetic modifications in gestational diabetes: new insights and possible pathophysiological connections

Franzago, Marica; Fraticelli, Federica; Marchioni, Michele; Nicola, Marta Di; Sebastiano, F. Di; Liberati, Marco; Stuppia, Liborio; Vitacolonna, Ester

doi:10.1007/s00592-020-01668-5

Cited by 18 publications

(12 citation statements)

References 80 publications

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“…Furthermore, for participants with the FTO risk allele (AA), the expression of miR-22-5p was downregulated. One known target of miR-22 is the histone deacetylase 4 ( HDAC4 ) [ 39 ], supporting the theory that metabolic phenotypes are probably mediated by epigenetic mechanisms due to the different FTO mutations [ 40 ]. These results highlight the importance of personalized analysis and interventions, as the epigenetic phenotype varies significantly depending on the genotype.…”

Section: Discussionmentioning

confidence: 92%

MiRNA-based “fitness score” to assess the individual response to diet, metabolism, and exercise

Krammer

Tschida

Berner

et al. 2022

Journal of the International Society of Sports Nutrition

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Background Regular, especially sustained exercise plays an important role in the prevention and treatment of multiple chronic diseases. Some of the underlying molecular and cellular mechanisms behind the adaptive response to physical activity are still unclear, but recent findings suggest a possible role of epigenetic mechanisms, especially miRNAs, in the progression and management of exercise-related changes. Due to the combination of the analysis of epigenetic biomarkers (miRNAs), the intake of food and supplements, and genetic dispositions, a “fitness score” was evaluated to assess the individual response to nutrition, exercise, and metabolic influence. Methods In response to a 12-week sports intervention, we analyzed genetic and epigenetic biomarkers in capillary blood from 61 sedentary, healthy participants (66.1% females, 33.9% males, mean age 33 years), including Line-1 methylation, three SNPs, and ten miRNAs using HRM and qPCR analysis. These biomarkers were also analyzed in a healthy, age- and sex-matched control group (n, 20) without intervention. Food frequency intake, including dietary supplement intake, and general health questionnaires were surveyed under the supervision of trained staff. Results Exercise training decreased the expression of miR-20a-5p, −22-5p, and −505-3p (p < 0.02) and improved the “fitness score,” which estimates eight different lifestyle factors to assess, nutrition, inflammation, cardiovascular fitness, injury risk, regeneration, muscle and hydration status, as well as stress level. In addition, we were able to determine correlations between individual miRNAs, miR-20a-5p, −22-5p, and −101-3p (p < 0.04), and the genetic predisposition for endurance and/or strength and obesity risk ( ACE, ACTN3 , and FTO ), as well as between miRNAs and the body composition (p < 0.05). MiR-19b-3p and −101-3p correlated with the intake of B vitamins. Further, miR-19b-3p correlated with magnesium and miR-378a-3p with iron intake (p < 0.05). Conclusions In summary, our results indicate that a combined analysis of several biomarkers (miRNAs) can provide information about an individual’s training adaptions/fitness, body composition, nutritional needs, and possible recovery. In contrast to most studies using muscle biopsies, we were able to show that these biomarkers can also be measured using a minimally invasive method.

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Section: Discussionmentioning

confidence: 92%

MiRNA-based “fitness score” to assess the individual response to diet, metabolism, and exercise

Krammer

Tschida

Berner

et al. 2022

Journal of the International Society of Sports Nutrition

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“… No data on foetal sex Sletner et al, 2021 [ 90 ] 33 GDM 27 Ctrl PS FTO No association between FTO DNAm and GDM. No data on foetal sex Franzago et al, 2021 [ 91 ] 23 GDM 23 Ctrl MethylTarget Technique MEG3 DNAm was increased in GDM, and positively associated with birthweight and fasting glucose levels. No data on foetal sex Chen et al, 2021 [ 92 ] 20 GDM 16 Ctrl 450k EWAS 662 CpGs with differential DNAm in GDM (without FDR).…”

Section: Introductionmentioning

confidence: 99%

Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps

et al. 2022

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SUMMARY Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in pregnancies complicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy outcome, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in pregnancies complicated by diabetes and obesity.

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“…In vitro , FTO efficiently eliminated the m6A modification of mRNA ( 56 ). Recently, some studies have found strong associations between FTO and hypertension ( 57 ), diabetes ( 58 , 59 ), obesity ( 60 , 61 ), non-alcoholic fatty liver disease ( 62 , 63 ), atherosclerosis ( 64 ), myocardial infarction ( 38 , 65 ), ischemic reperfusion injury ( 65 ), cardiac hypertrophy ( 65 ), and heart failure ( 65 ). Thus, FTO considerably contributes to the progression of cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease

Chen¹,

Xiong²,

Sun³

et al. 2022

Ann Transl Med

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Background: Several human diseases are associated with aberrant expression of regulators involved in N6methyladenosine (m6A) RNA modification. However, their role in aortic valve calcification (AVC) is largely unknown. The aim of this study was to determine the general expression pattern and potential function of m6A regulators in AVC by bioinformatics methods. Methods:We obtained AVC datasets from the Gene Expression Omnibus (GEO). The identification of m6Arelated differentially expressed genes (DEGs) and the Consensus Clustering method was performed to type AVC individuals based DEGs. Then, we quantified the effect of typing by principal component analysis (PCA). Next, we performed the weighted gene co-expression network analysis (WGCNA) and identified the main modules as well as functional analysis. Additionally, the key genes were screened by protein-protein interaction network (PPIN) analysis and identifying important genes of important modules. We again typed AVC individuals by the same method using key genes. Finally, we evaluated the link between key genes and immune infiltration.Results: We discovered that METTL14, ZC3H13, FTO, FMR1, HNRNPA2B1, HNRNPC, LRPPRC, YTHDC1, YTHDC2, and YTHDF1 expression levels decreased considerably in AVC tissues. Based on 10 genes, we typed 240 AVC samples as clusters A and B. We assessed the immune cell content in 240 samples using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and found that B cell memory, CD8 T cells, T follicular helper cells, monocytes, M0 macrophages, resting dendritic cells (DCs), and interleukin-10 (IL-10) were concentrated in the cluster A group. Additionally, based on the important WGCNA modules, we identified 7 key genes. Next, 240 samples were retyped based on 7 key genes; we found that T cells CD8, T cells CD4 memory activated, T cells follicular helper, and macrophages M1 were significantly increased in gene cluster-1. Finally, we performed functional enrichment of gene cluster-typed samples, showing potential functional differences between different types. Conclusions:Our study provides a review of the m6A regulators' expression pattern and functional importance in human AVC. The data from this study might serve as a significant resource for future mechanistic and therapeutic investigations into the role of critical m6A regulators in AVC.

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Fat mass and obesity-associated (FTO) gene epigenetic modifications in gestational diabetes: new insights and possible pathophysiological connections

Cited by 18 publications

References 80 publications

MiRNA-based “fitness score” to assess the individual response to diet, metabolism, and exercise

MiRNA-based “fitness score” to assess the individual response to diet, metabolism, and exercise

Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps

Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease

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