Epigenetics and Epigenomics: Implications for Diabetes and Obesity

Rosen, Evan D.; Kaestner, Klaus H.; Natarajan, Rama; Patti, Mary‐Elizabeth; Sallari, Richard; Sander, Maike; Suszták, Katalin

doi:10.2337/db18-0537

Cited by 141 publications

(90 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies of diet induced obesity in mice identified persistent insulin resistance following short-term weight loss (22,36,37). Persistent epigenetic alterations have also previously been proposed as a "molecular memory" mechanism in gluconormalized diabetics with an increased risk for retinopathy and additional microvascular complications (38,39). Taken together, these studies and our present work suggest that obesityinduced changes to DNA methylation at loci associated with energy homeostasis may be involved in unresolved metabolic adaptation, or epigenetic "memory" following weight loss.…”

Section: Discussionsupporting

confidence: 76%

DNA Methylation Changes More Slowly Than Physiological States in Response to Weight Loss in Genetically Diverse Mouse Strains

et al. 2019

View full text Add to dashboard Cite

Responses to a high fat, high sucrose (HFHS) diet vary greatly among inbred strains of mice. We sought to examine the epigenetic (DNA methylation) changes underlying these differences as well as variation in weight loss when switched to a low-fat chow diet. We surveyed DNA methylation from livers of 45 inbred mouse strains fed a HFHS diet for 8 weeks using reduced-representation bisulfite sequencing (RRBS). We observed a total of 1,045,665 CpGs of which 83 candidate sites were significantly associated with HFHS diet. Many of these CpGs correlated strongly with gene expression or clinical traits such as body fat percentage and plasma glucose. Five inbred strains were then studied in the context of weight loss to test for evidence of epigenetic "memory." The mice were first fed a HFHS diet for 6 weeks followed by a low-fat chow diet for 4 weeks. Four of the five strains returned to initial levels of body fat while one strain, A/J, retained almost 50% of the fat gained. A total of 36 of the HFHS diet responsive CpGs exhibited evidence of persistent epigenetic modifications following weight normalization, including CpGs near the genes Scd1 and Cdk1. Our study identifies DNA methylation changes in response to a HFHS diet challenge that revert more slowly than overall body fat percentage in weight loss and provides evidence for epigenetic mediated "memory."

show abstract

Section: Discussionsupporting

confidence: 76%

DNA Methylation Changes More Slowly Than Physiological States in Response to Weight Loss in Genetically Diverse Mouse Strains

et al. 2019

View full text Add to dashboard Cite

show abstract

“…There are different epigenetic regulation mechanisms: direct methylation of cytosine or adenine residues, covalent modifications of histone proteins, higher-order chromatin structure and non-coding RNAs. Disruptions or imbalances in epigenetic mechanisms can lead to the development of diabetic pathophysiology [ 90 ].…”

Section: Mechanisms Leading To T2dm and Pathophysiologymentioning

confidence: 99%

Pathophysiology of Type 2 Diabetes Mellitus

Galicia-García

Benito‐Vicente

Jebari

et al. 2020

IJMS

1,737

822

View full text Add to dashboard Cite

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.

show abstract

“…Glycine also participates in the regulation of pH, nucleotide synthesis and methylation [77,84,85]. Lower levels of glycine may therefore lead to epigenetic modifications in embryos, which have been described in diabetic pregnancies [86,87].…”

Section: Amino Acid Metabolism Is Differently Regulated In the Maternmentioning

confidence: 99%

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Schindler

Pendzialek

Grybel

et al. 2020

IJMS

View full text Add to dashboard Cite

Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.

show abstract

Epigenetics and Epigenomics: Implications for Diabetes and Obesity

Cited by 141 publications

References 61 publications

DNA Methylation Changes More Slowly Than Physiological States in Response to Weight Loss in Genetically Diverse Mouse Strains

DNA Methylation Changes More Slowly Than Physiological States in Response to Weight Loss in Genetically Diverse Mouse Strains

Pathophysiology of Type 2 Diabetes Mellitus

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits

Contact Info

Product

Resources

About