Epigenetics and Metabolism

Keating, Samuel T.; El‐Osta, Assam

doi:10.1161/circresaha.116.303936

Cited by 250 publications

(203 citation statements)

References 247 publications

Supporting

Mentioning

198

Contrasting

Order By: Relevance

“…Many epigenetic regulators require metabolically-derived intermediates to perform their functions [54]. Acetyl-CoA is used as a substrate for HATs , α-ketoglutarate and flavin adenine dinucleotide are TET and histone lysine demethylase (KDM) co-factors, and nicotinamide adenine dinucleotide is required for SIRT-dependent histone deacetylation [54].…”

Section: Metabolismmentioning

confidence: 99%

“…Acetyl-CoA is used as a substrate for HATs , α-ketoglutarate and flavin adenine dinucleotide are TET and histone lysine demethylase (KDM) co-factors, and nicotinamide adenine dinucleotide is required for SIRT-dependent histone deacetylation [54]. In skeletal muscle, satellite cells transition from fatty acid oxidation to glycolysis during activation, leading to decreased nicotinamide adenine dinucleotide and reduced SIRT1 deacetylase activity [55].…”

Section: Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Resetting the epigenome for heart regeneration.

Quaife-Ryan

Sim

Porrello

et al. 2016

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyoctes following modulation of these factors rarely reaches neonatal levels. The inefficient re-induction of proliferation in adult cardiomyocytes may be due to the epigenetic landscape, which drastically changes during cardiac development and maturation. In this review, we provide an overview of the role of epigenetic modifiers in developmental processes related to cardiac regeneration. We propose an epigentic framework for heart regeneration whereby adult cardiomyocyte identity requires resetting to a neonatal-like state to facilitate cell cycle re-entry and regeneration following cardiac injury.

show abstract

Section: Metabolismmentioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

Resetting the epigenome for heart regeneration.

Quaife-Ryan

Sim

Porrello

et al. 2016

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

show abstract

“…Given the additional observation that metabolic signals can trigger epigenetic modifications, which can persist across cell division (11,12), epigenetic modifications represent attractive candidates for mediating this metabolic memory. However, because epigenetic modifications can be dynamic and reversible, characterizing persistent versus transient chromatin changes in response to metabolic signaling is a major challenge for the field (13).…”

mentioning

confidence: 99%

Persistent Chromatin Modifications Induced by High Fat Diet*

Leung

Trac

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Obesity is a highly heritable complex disease that results from the interaction of multiple genetic and environmental factors. Formerly obese individuals are susceptible to metabolic disorders later in life, even after lifestyle changes are made to mitigate the obese state. This is reminiscent of the metabolic memory phenomenon originally observed for persistent complications in diabetic patients, despite subsequent glycemic control. Epigenetic modifications represent a potential mediator of this observed memory. We previously demonstrated that a high fat diet leads to changes in chromatin accessibility in the mouse liver. The regions of greatest chromatin changes in accessibility are largely strain-dependent, indicating a genetic component in diet-induced chromatin alterations. We have now examined the persistence of diet-induced chromatin accessibility changes upon diet reversal in two strains of mice. We find that a substantial fraction of loci that undergo chromatin accessibility changes with a high fat diet remains in the remodeled state after diet reversal in C57BL/6J mice. In contrast, the vast majority of dietinduced chromatin accessibility changes in A/J mice are transient. Our data also indicate that the persistent chromatin accessibility changes observed in C57BL/6J mice are associated with specific transcription factors and histone post-translational modifications. The persistent loci identified here are likely to be contributing to the overall phenotype and are attractive targets for therapeutic intervention.Obesity and related metabolic diseases result from both genetic and environmental factors, such as exercise and diet. However, the molecular mechanisms that contribute to disease progression remain unclear. Intriguingly, previously obese individuals have increased mortality compared with normal individuals, despite therapeutic intervention (1). This is reminiscent of "metabolic memory," a phenomenon originally described in diabetic patients in which micro-and macrovascular complications develop long after blood glucose is normalized (2-4). It has been hypothesized that epigenetic modifications, such as alterations to the chromatin and non-sequence changes to DNA, including DNA methylation, can contribute to this "metabolic memory" (5-7).It is now well established that epigenetic modifications can contribute to disease progression (8). One manner by which external environmental factors can influence molecular pathways is through alterations to chromatin. It has been shown that high fat (HF) 2 diet leads to chromatin accessibility changes in the liver tissue of mice (9). Intriguingly, the genomic loci with the greatest degree of diet-induced chromatin accessibility changes are largely strain-specific, indicating a role for genetics in this response (9). Previous studies examining diet-induced metabolic dysfunctions have shown that mice that transition from HF to diets that are low in fats do not completely revert to the same state as mice only maintained on low fat diets (10). The data indicate th...

show abstract

“…The number of reviews on the topic of linking epigenetic modifications to obesity and T2D seems convincingly huge, e.g. [157][158][159][160][161][162][163][164][165][166][167].…”

Section: Histones In Human Adipocytesmentioning

confidence: 99%

Human Adipocytes : Proteomic Approaches

Jufvas¹

2016

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Type 2 diabetes is characterized by increased levels of glucose in the blood originating from insulin resistance in insulin sensitive tissues and from reduced pancreatic insulin production. Around 400 million people in the world are diagnosed with type 2 diabetes and the correlation with obesity is strong. In addition to life style induction of obesity and type 2 diabetes, there are indications of genetic and epigenetic influences. This thesis has focused on the characterization of primary human adipocytes, who play a crucial role in the development of type 2 diabetes. Histones are important proteins in chromatin dynamics and may be one of the factors behind epigenetic inheritance. In paper I, we characterized histone variants and posttranslational modifications in human adipocytes. Several of the specific posttranslational histone modifications we identified have been characterized in other cell types, but the majority was not previously known. Moreover, we identified a variant of histone H4 on protein level for the first time. In paper II, we studied specific histone H3 methylations in the adipocytes. We found that overweight is correlated with a reduction of H3K4me2 while type 2 diabetes is associated with an increase of H3K4me3. This shows a genome-wide difference in important chromatin modifications that could help explain the epidemiologically shown association between epigenetics and metabolic health. Caveolae is a plasma membrane structure involved in the initial and important steps of insulin signaling. In paper III we characterized the IQGAP1 interactome in human adipocytes and suggest that IQGAP1 is a link between caveolae and the cytoskeleton. Moreover, the amount of IQGAP1 is drastically lower in adipocytes from type 2 diabetic subjects compared with controls implying a potential role for IQGAP1 in insulin resistance. In conclusion, this thesis provides new insights into the insulin signaling frameworks and the histone variants and modifications of human adipocytes

show abstract

Epigenetics and Metabolism

Cited by 250 publications

References 247 publications

Resetting the epigenome for heart regeneration.

Resetting the epigenome for heart regeneration.

Persistent Chromatin Modifications Induced by High Fat Diet*

Human Adipocytes : Proteomic Approaches

Contact Info

Product

Resources

About