Nutritional programming of the metabolic syndrome

Symonds, Michael; Sebért, Sylvain; Hyatt, Melanie A.; Budge, Helen

doi:10.1038/nrendo.2009.195

Cited by 327 publications

(254 citation statements)

References 85 publications

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“…Given that brain methylation cannot be studied in vivo in humans, and that epigenetic changes relevant for developmental programming can be part of a general response of the entire organism, 20,37 we used pyrosequencing to analyze rs6265 methylation in peripheral blood mononuclear cells (PBMCs) of 259 healthy humans. This site is differentially methylated in human PBMCs and, as predictable, methylation was affected by rs6265 genotype, given that only the Val allele has a CpG in this position (ANOVA: ND259; F 2,256 D1601.2; P < 0.001 ÃÃÃ ; ValVal > ValMet > MetMet; Fig.…”

Section: Resultsmentioning

confidence: 99%

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

et al. 2016

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Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val 66 Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.

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Section: Resultsmentioning

confidence: 99%

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

et al. 2016

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“…Classic examples include fetal programming effects, such as maternal stress or undernutrition leading to fetal growth retardation, compromises in fetal cerebral development, catch-up growth, and early onset of insulin resistance and adult cardiometabolic diseases (1,2,45,46). It has been suggested that telomere length may, in part, underlie this association (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

346

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Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.developmental programming | fetal origin

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“…The fetal or developmentally programmed genesis of adult sickness hypothesis settled that environmental factors and maternal lifestyles, particularly adverse nutritional disturbances, proceed in early life to drive the risks for the onset of metabolic diseases and excessive weight gain in later life stages (23) . Indeed, maternal nutrition can programme gene expression patterns to the embryo that persist into adulthood and may contribute to the appearance of typical metabolic syndrome features such as hypertension, insulin resistance, hyperlipaemia and abdominal obesity (24) . The parental conditions and lifestyles, which may involve maternal size/obesity, famine at perinatal periods, the use of nutritional supplements, alcohol or drug abuse as well as the administration of therapeutical agents in this critical period may alter specific processes with an impact on embryonic, placental and fetal growth, organogenesis or regulatory set points for system functions affecting adiposity, where inflammatory and immunologically mediated processes may be involved (25) .…”

Section: The Developmental Origins Of Health and Disease Hypothesis Amentioning

confidence: 99%

Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes

et al. 2012

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The huge health burden accompanying obesity is not only attributable to inadequate dietary and sedentary lifestyle habits, since a predisposing genetic make-up and other putative determinants concerning easier weight gain and fat deposition have been reported. Thus, several investigations aiming to understand energy metabolism and body composition maintenance have been performed considering the participation of perinatal nutritional programming and epigenetic processes as well as inflammation phenomena. The Developmental Origins of Health and Disease hypothesis and inheritance-oriented investigations concerning gene-nutrient interactions on energy homoeostasis and metabolic functions have suggested that inflammation could be not only a comorbidity of obesity but also a cause. There are several examples about the role of nutritional interventions in pregnancy and lactation, such as energetic deprivation, protein restriction and excess fat, which determine a cluster of disorders affecting energy efficiency in the offspring as well as different metabolic pathways, which are mediated by epigenetics encompassing the chromatin information encrypted by DNA methylation patterns, histone covalent modifications and non-coding RNA or microRNA. Epigenetic mechanisms may be boosted or impaired by dietary and environmental factors in the mother, intergenerationally or transiently transmitted, and could be involved in the obesity and inflammation susceptibility in the offspring. The aims currently pursued are the early identification of epigenetic biomarkers concerned in individual's disease susceptibility and the description of protocols for tailored dietary treatments/advice to counterbalance adverse epigenomic events. These approaches will allow diagnosis and prognosis implementation and facilitate therapeutic strategies in a personalised 'epigenomically modelled' manner to combat obesity and inflammation.

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Nutritional programming of the metabolic syndrome

Cited by 327 publications

References 85 publications

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes

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