Role of Epigenetics in Type 2 Diabetes and Obesity.
Ontology highlight
ABSTRACT:
SUBMITTER: Capparelli R
PROVIDER: S-EPMC8393970 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Purpose of reviewEpigenetics is defined as mitotically heritable changes in gene expression that do not directly alter the DNA sequence. By implication, such epigenetic changes are non-genetically determined, although they can be affected by inherited genetic variation. Extensive evidence indicates that autoimmune diseases including type 1 diabetes are determined by the interaction of genetic and non-genetic factors. Much is known of the genetic causes of these diseases, but the non-genetic effects are less clear-cut. Further, it remains unclear how they interact to cause the destructive autoimmune process. This review identifies the key issues in the genetic/non-genetic interaction, examining the most recent evidence of the role of non-genetic effects in the disease process, including the impact of epigenetic effects on key pathways.Recent findingsRecent research indicates that these pathways likely involve immune effector cells both of the innate and adaptive immune response. Specifically, there is evidence of cell type-specific enrichment in altered DNA methylation, changes which were temporally stable and enriched at gene regulatory elements. Epigenomics remains in its infancy, and we anticipate further studies will define how the interaction of genetic and non-genetic effects induces tissue-specific destruction and enhances our ability to predict, and possibly even modify that process.
| S-EPMC5559569 | biostudies-literature
Project description:The American Diabetes Association convened a research symposium, "Epigenetics and Epigenomics: Implications for Diabetes and Obesity" on 17-19 November 2017. International experts in genetics, epigenetics, computational biology, and physiology discussed the current state of understanding of the relationships between genetics, epigenetics, and environment in diabetes and examined existing evidence for the role of epigenetic factors in regulating metabolism and the risk of diabetes and its complications. The authors summarize the presentations, which highlight how the complex interactions between genes and environment may in part be mediated through epigenetic changes and how information about nutritional and other environmental stimuli can be transmitted to the next generation. In addition, the authors present expert consensus on knowledge gaps and research recommendations for the field.
| S-EPMC6463748 | biostudies-literature
Project description:Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40-70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these variants do not fully explain the heritability of obesity, other forms of variation, such as epigenetics marks, must be considered. Epigenetic marks, or "imprinting", affect gene expression without actually changing the DNA sequence. Failures in imprinting are known to cause extreme forms of obesity (e.g. Prader-Willi syndrome), but have also been convincingly associated with susceptibility to obesity. Furthermore, environmental exposures during critical developmental periods can affect the profile of epigenetic marks and result in obesity. We review the most recent evidence for genetic and epigenetic mechanisms involved in the susceptibility and development of obesity. Only a comprehensive understanding of the underlying genetic and epigenetic mechanisms, and the metabolic processes they govern, will allow us to manage, and eventually prevent, obesity.
| S-EPMC3213306 | biostudies-literature
Project description:Bariatric surgery has emerged as a viable treatment option in morbidly obese individuals with type 2 diabetes. Concomitant with societal lifestyle changes and the increased emphasis on achieving metabolic targets, there has been a rise in the number of patients with type 1 diabetes (T1DM) who are overweight and obese. Preliminary experience based on a limited number of observational reports points to substantial weight loss and amelioration of comorbid conditions such as blood pressure and dyslipidemia in patients with T1DM who undergo weight loss surgery. However, there is little evidence to suggest significant improvement in glycemic control and lowering of glycosylated hemoglobin, and bariatric surgical procedures do not necessarily lead to enhanced diabetes management. and improved quality of life. The potential possibility of micronutrient deficiency, weight regain, and psychobehavioral issues post-bariatric surgery also exists. An individualized evaluation of the risks and benefits should be considered, using a a multidisciplinary team approach with expertise in patient selection, surgical technique, and follow-up. A crucial component is the availability of a diabetes care specialist or endocrinologist experienced in intensive, tailored, modifiable insulin regimens who maintains close and careful monitoring during all phases of management. Reliable data from a prospective, longitudinal perspective is required to provide guidelines for clinicians and informed choices for obese patients with T1DM who are contemplating bariatric surgery.
| S-EPMC4936488 | biostudies-literature
Project description:Peroxisome proliferator-activated receptor gamma (PPAR?) is a nuclear receptor that is deregulated in obesity. PPAR? exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPAR? and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPAR?. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPAR? promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPAR? level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPAR?. A significant negative correlation was found between PPAR? levels and the studied microRNAs. There was a significant PPAR? promoter hypermethylation in CRC patients that correlated to low PPAR? levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPAR? downregulation. Hypermethylation of PPAR? gene promoter is associated with CRC through suppression of PPAR? regardless of BMI.
| S-EPMC5587696 | biostudies-literature
Project description:Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual's risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.
| S-EPMC9670650 | biostudies-literature
Project description:The risk of type 2 diabetes (T2D) increases with obesity. One possible explanation is that pleiotropic genes affect risk of both T2D and obesity. To identify pleiotropic genes, we performed bivariate analysis of T2D with waist-hip ratio (WHR) and with body mass index (BMI) in the African-American subset of the Genetics of NIDDM (GENNID) sample. Of 12 T2D loci identified through suggestive or higher univariate logarithm of the odds ratio (lod) scores, we inferred pleiotropy with obesity for six (chromosomes 1 at 17-19?Mb, 2 at 237-240?Mb, 7 at 54-73?Mb, 13 at 26-30?Mb, 16 at 26-47?Mb and 20 at 56-59?Mb). These findings provide evidence that at least some of the co-occurrence of obesity with T2D is because of pleiotropic genes. We also inferred four obesity loci through suggestive or higher lod scores for WHR (chromosomes 1 at 24-32?Mb, 2 at 79-88?Mb, 2 at 234-238?Mb and 3 at 148-159?Mb).
| S-EPMC3143214 | biostudies-literature
Project description:Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling ?-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on ?-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.
| S-EPMC5501211 | biostudies-literature
Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls.
2023-06-23 | PXD036423 | Pride
Project description:Nowadays, there is still a popular belief that dietary sugars, in particular sucrose, are directly linked to the development of type 2 diabetes mellitus (T2DM). Furthermore, since insulin action is impaired in T2DM, it is still believed that excluding dietary sugars from the diet can adequately treat T2DM. This might be based on the assumption that dietary sugars have a stronger impact on blood glucose levels than other carbohydrates. Therefore, the aim of this review is to discuss the effects of dietary sugars intake, including sugar-sweetened beverages (SSBs) against the background of overall energy intake and weight gain in the development of T2DM. Furthermore, the effect of dietary sugars, including SSBs on glycemic control will be discussed. Results from various systematic reviews and meta-analyses do not support the idea that the intake of sucrose and other dietary sugars is linked to T2DM. Long-chain or complex carbohydrates can have a greater impact on postprandial glycemic response than sucrose. SSBs do not affect glycemic control if substituted for other calorie sources. Current scientific evidence clearly points toward excess energy intake followed by excess body fat gain being most relevant in the development of T2DM.
| S-EPMC9630103 | biostudies-literature