Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes

AbstractSixteen-week-old female C57BL/6J mice were sacrificed aboard the International Space Station after 37 days of flight (RR-1 mission) and frozen carcasses returned to Earth. RNA was isolated from interscapular brown adipose tissue (BAT) and gonadal white adipose tissue (WAT). Spaceflight resulted in differential expression of genes in BAT consistent with increased non-shivering thermogenesis and differential expression of genes in WAT consistent with increased glucose uptake and metabolism, adipogenesis, and β-oxidation.

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Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes

PLoS ONE ◽

10.1371/journal.pone.0189153 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0189153 ◽

Cited By ~ 9

Author(s):

Sandra Rodríguez-Rodero ◽

Edelmiro Menéndez-Torre ◽

Gustavo Fernández-Bayón ◽

Paula Morales-Sánchez ◽

Lourdes Sanz ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Adipose Tissue

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Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1150-7446 ◽

2020 ◽

Author(s):

Helen Sievert ◽

Christin Krause ◽

Cathleen Geißler ◽

Martina Grohs ◽

Alexander T. El-Gammal ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Fatty Acids ◽

Adipose Tissue ◽

Glucose Intolerance ◽

Visceral Adipose Tissue ◽

High Hba1c ◽

Obese Subjects ◽

Visceral Adipose

Abstract Objective The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN (fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits. Subjects and methods Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing. Results FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (SCD, ELOVL6) or lipolytic genes (ADRB3, PNPLA2) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = − 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005). Conclusions Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.

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Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets

Environmental Epigenetics ◽

10.1093/eep/dvz015 ◽

2019 ◽

Vol 5 (3) ◽

Cited By ~ 3

Author(s):

Ge Li ◽

Tihomira D Petkova ◽

Eleonora Laritsky ◽

Noah Kessler ◽

Maria S Baker ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Pancreatic Islets ◽

Cell Function ◽

Control Male ◽

Small Litter ◽

Endoplasmic Reticulum Calcium ◽

Expression Of Genes ◽

Β Cell Function

Abstract Pancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation. We performed genome-scale DNA methylation profiling in islets from postnatally over-nourished (suckled in a small litter) and control male mice at both postnatal day 21 and postnatal day 180. DNA methylation differences were validated using quantitative bisulfite pyrosequencing, and associations with expression were assessed by RT-PCR. We discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging (R2 = 0.33, P < 0.0001). These methylation differences were inversely correlated with mRNA expression of genes relevant to β cell function [including Rab3b (Ras-related protein Rab-3B), Cacnb3 (voltage-dependent L-type calcium channel subunit 3), Atp2a3 (sarcoplasmic/endoplasmic reticulum calcium ATPase 3) and Ins2 (insulin 2)]. Relative to control, small litter islets showed DNA methylation differences directly after weaning and in adulthood, but few of these were present at both ages. Surprisingly, we found substantial overlap of methylated loci caused by aging and small litter feeding, suggesting that the age-associated gain of DNA methylation happened much earlier in small litter islets than control islets. Our results provide the novel insights that aging-associated DNA methylation increases reflect an epigenetic drift toward the exocrine pancreas epigenome, and that early postnatal overnutrition may accelerate this process.

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The Impact of Exercise on DNA Methylation of Genes Associated with Type 2 Diabetes and Obesity in Human Adipose Tissue

US Endocrinology ◽

10.17925/use.2014.10.01.64 ◽

2014 ◽

Vol 10 (01) ◽

pp. 64 ◽

Cited By ~ 2

Author(s):

Tina Rönn ◽

Charlotte Ling ◽

◽

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Adipose Tissue ◽

Human Adipose Tissue ◽

Short Review ◽

Methylation Pattern ◽

Cellular Level ◽

Genetic And Environmental Factors ◽

The Impact

It is well established that exercise promotes health, and reduces people’s risks for developing type 2 diabetes and becoming obese. But just how exercise performs this, at a cellular level, and what molecular and physiologic steps are involved and in what order, are still not fully understood. Metabolic disorders are often influenced by interactions between genetic and environmental factors. One possible explanation for how the environment may influence the genome is through epigenetic mechanisms–that is–chemical modifications to the DNA itself. Epigenetic factors include, for example, DNA methylation, histone modifications, and different RNA-mediated processes, which all have the ability to bind to DNA or affect the chromatin structure and thereby change how specific genes are interpreted and expressed. In this short review, we focus on describing how exercise influences the genome-wide DNA methylation pattern, including candidate genes for obesity and type 2 diabetes, in human adipose tissue.

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