Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men.

: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells.

Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children.

Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip.

Human adipogenesis is associated with genome-wide DNA methylation and gene-expression changes.

Aim: To define the genomic distribution and function of DNA methylation changes during human adipogenesis.

Methods: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes.

Results: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830 transcripts after differentiation.

Epigenetic programming of adipose-derived stem cells in low birthweight individuals.

Aims/hypothesis: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals.

Methods: ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men.

A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits.

Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years.

Genome-wide associations between genetic and epigenetic variation influence mRNA expression and insulin secretion in human pancreatic islets.

Genetic and epigenetic mechanisms may interact and together affect biological processes and disease development. However, most previous studies have investigated genetic and epigenetic mechanisms independently, and studies examining their interactions throughout the human genome are lacking. To identify genetic loci that interact with the epigenome, we performed the first genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human pancreatic islets.

Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion.

Impaired insulin secretion is a hallmark of type 2 diabetes (T2D). Epigenetics may affect disease susceptibility. To describe the human methylome in pancreatic islets and determine the epigenetic basis of T2D, we analyzed DNA methylation of 479,927 CpG sites and the transcriptome in pancreatic islets from T2D and non-diabetic donors.

A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue.

Epigenetic mechanisms are implicated in gene regulation and the development of different diseases. The epigenome differs between cell types and has until now only been characterized for a few human tissues. Environmental factors potentially alter the epigenome.

Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.

Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.

Regulation of core clock genes in human islets.

Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose.

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

Objective: Gene 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 Methods: Gene expression was analyzed in human pancreatic islets from 55 non-diabetic donors and nine T2D donors using microarray.

The expression of myosin heavy chain (MHC) genes in human skeletal muscle is related to metabolic characteristics involved in the pathogenesis of type 2 diabetes.

Type 2 diabetes patients exhibit a reduction in oxidative muscle fibres and an increase in glycolytic muscle fibres. In this study, we investigated whether both genetic and non-genetic factors influence the mRNA expression levels of three myosin heavy chain (MHC) genes represented in different fibre types. Specifically, we examined the MHC7 (slow-twitch oxidative fibre), MHCIIa (fast-twitch oxidative fibre) and MHCIIx/d (fast-twitch glycolytic fibre) genes in human skeletal muscle.

Two common genetic variants near nuclear-encoded OXPHOS genes are associated with insulin secretion in vivo.

Context: Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the β-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes.

Objective: The aim of this study was to identify genetic loci in or adjacent to nuclear-encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo.

A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes.

Type 2 diabetes (T2D) evolves when insulin secretion fails. Insulin release from the pancreatic β cell is controlled by mitochondrial metabolism, which translates fluctuations in blood glucose into metabolic coupling signals. We identified a common variant (rs950994) in the human transcription factor B1 mitochondrial (TFB1M) gene associated with reduced insulin secretion, elevated postprandial glucose levels, and future risk of T2D.

A common variant near the PRL gene is associated with increased adiposity in males.

A common variant (rs4712652) adjacent to the prolactin gene was recently associated with obesity using a genome-wide association study. The aim of this study was to replicate the association between rs4712652 and obesity and further examine if rs4712652 is associated with fat percentage and adiponectin levels in a population based Scandinavian cohort. rs4712652 was genotyped in 4879 participants (mean BMI 26.