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Journal ArticleDOI

Epigenomics, gestational programming and risk of metabolic syndrome

02 Feb 2015-International Journal of Obesity (Int J Obes (Lond))-Vol. 39, Iss: 4, pp 633-641
TL;DR: The evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome is discussed.
Abstract: Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.
Citations
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Journal ArticleDOI
TL;DR: The aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children.

409 citations


Cites background from "Epigenomics, gestational programmin..."

  • ...…evidence that show that the increased presence of EDCs in the environment may also explain an important part of the incidence of metabolic disorders in humans, including obesity, insulin resistance, type 2 diabetes, hepatic injury, dyslipidemia and cardiovascular diseases (Desai et al., 2015)....

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Journal Article
TL;DR: The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the "programming phenotype" and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.
Abstract: Epidemiological studies linking low birth weight and subsequent cardiometabolic disease have given rise to the hypothesis that events in fetal life permanently program subsequent cardiovascular risk. The effects of fetal programming may not be limited to the first-generation offspring. We have explored intergenerational effects in the dexamethasone-programmed rat, a model in which fetal exposure to excess glucocorticoid results in low birth weight with subsequent adult hyperinsulinemia and hyperglycemia underpinned by increased activity of the key hepatic gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). We found that the male offspring of female rats that had been exposed prenatally to dexamethasone, but were not manipulated in their own pregnancy, also had reduced birth weight (5.66 ± 0.06 vs. 6.12 ± 0.06 g, P < 0.001), glucose intolerance, and elevated hepatic PEPCK activity (5.7 ± 0.6 vs. 3.3 ± 0.2 nmol.min -1 .mg protein -1 , P < 0.001). These effects resolved in a third generation. Similar intergenerational programming was observed in offspring of male rats exposed prenatally to dexamethasone mated with control females. The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the programming phenotype and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.

352 citations

Journal ArticleDOI
TL;DR: The role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action are discussed.
Abstract: The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes.

298 citations

Journal ArticleDOI
TL;DR: In this article, the authors provide a thorough overview of the advanced membrane-based treatment methods available for the effective removal of organic micropollutants (MPs) in water and wastewater.

202 citations

Journal ArticleDOI
TL;DR: This critical review of existing theories explaining the evolutionary origins of obesity and novel biological and sociocultural agents of evolutionary change to help explain the modern‐day distribution of obesity‐predisposing variants are appraised.
Abstract: Genetic predisposition to obesity presents a paradox: how do genetic variants with a detrimental impact on human health persist through evolutionary time? Numerous hypotheses, such as the thrifty genotype hypothesis, attempt to explain this phenomenon yet fail to provide a justification for the modern obesity epidemic. In this critical review, we appraise existing theories explaining the evolutionary origins of obesity and explore novel biological and sociocultural agents of evolutionary change to help explain the modern-day distribution of obesity-predisposing variants. Genetic drift, acting as a form of 'blind justice,' may randomly affect allele frequencies across generations while gene pleiotropy and adaptations to diverse environments may explain the rise and subsequent selection of obesity risk alleles. As an adaptive response, epigenetic regulation of gene expression may impact the manifestation of genetic predisposition to obesity. Finally, exposure to malnutrition and disease epidemics in the wake of oppressive social systems, culturally mediated notions of attractiveness and desirability, and diverse mating systems may play a role in shaping the human genome. As an important first step towards the identification of important drivers of obesity gene evolution, this review may inform empirical research focused on testing evolutionary theories by way of population genetics and mathematical modelling.

148 citations


Cites background from "Epigenomics, gestational programmin..."

  • ...gene expression (53), leading to activation or silencing of genes and regulation of transcriptional activity (212,213)....

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  • ...when modifications are made at promoters or enhancers (212,213)....

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References
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Journal ArticleDOI
10 Aug 2001-Science
TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Abstract: Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a “histone code” that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.

9,309 citations

Journal ArticleDOI
26 Feb 2014-JAMA
TL;DR: Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults.
Abstract: Importance More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. Objective To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Design, Setting, and Participants Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. Main Outcomes and Measures In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). Results In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children ( P = .03) and women ( P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Conclusions and Relevance Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.

7,532 citations

Journal ArticleDOI
13 Oct 2004-JAMA
TL;DR: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery, and a substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.
Abstract: ContextAbout 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery.ObjectiveTo determine the impact of bariatric surgery on weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea).Data Sources and Study SelectionElectronic literature search of MEDLINE, Current Contents, and the Cochrane Library databases plus manual reference checks of all articles on bariatric surgery published in the English language between 1990 and 2003. Two levels of screening were used on 2738 citations.Data ExtractionA total of 136 fully extracted studies, which included 91 overlapping patient populations (kin studies), were included for a total of 22 094 patients. Nineteen percent of the patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64 years). Sex was not reported for 1537 patients (8%). The baseline mean body mass index for 16 944 patients was 46.9 (range, 32.3-68.8).Data SynthesisA random effects model was used in the meta-analysis. The mean (95% confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative mortality (≤30 days) in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch. Diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients.ConclusionsEffective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.

6,373 citations

Journal ArticleDOI
01 Feb 2012-JAMA
TL;DR: In 2009-2010, the prevalence of obesity was 35.5% among adult men and 35.8% amongadult women, with no significant change compared with 2003-2008, and trends in BMI were similar to obesity trends.
Abstract: Results In 2009-2010 the age-adjusted mean BMI was 28.7 (95% CI, 28.3-29.1) for men and also 28.7 (95% CI, 28.4-29.0) for women. Median BMI was 27.8 (interquartile range [IQR], 24.7-31.7) for men and 27.3 (IQR, 23.3-32.7) for women. The age-adjusted prevalence of obesity was 35.5% (95% CI, 31.9%-39.2%) among adult men and 35.8% (95% CI, 34.0%-37.7%) among adult women. Over the 12-year period from 1999 through 2010, obesity showed no significant increase among women overall (age- and race-adjusted annual change in odds ratio [AOR], 1.01; 95% CI, 1.00-1.03; P=.07), but increases were statistically significant for non-Hispanic black women (P=.04) and Mexican American women (P=.046). For men, there was a significant linear trend (AOR, 1.04; 95% CI, 1.02-1.06; P.001) over the 12-year period. For both men and women, the most recent 2 years (2009-2010) did not differ significantly (P=.08 for men and P=.24 for women) from the previous 6 years (20032008). Trends in BMI were similar to obesity trends.

5,333 citations

Journal ArticleDOI
19 Nov 2009-Nature
TL;DR: The first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors were presented in this article.
Abstract: DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.

4,266 citations

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Trending Questions (1)
What are the epigenetic changes that occur in metabolic syndrome?

The paper discusses that epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling, and regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype.