Epigenomics: maternal high‐fat diet exposure
            <i>in utero</i>
            disrupts peripheral circadian gene expression in nonhuman primates

Suter, Melissa; Bocock, Philip; Showalter, Lori; Hu, Min; Shope, Cynthia; McKnight, Robert A.; Grove, Kevin L.; Lane, Robert H.; Aagaard‐Tillery, Kjersti

doi:10.1096/fj.10-172080

Cited by 128 publications

(108 citation statements)

References 74 publications

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“…97 In utero exposure to maternal high-fat nutrition has been shown to upregulate the expression of fetal hepatic circadian-associated neuronal PAS domain protein 2, at least in part through hyperacetylation of histone H3 at lysine 14. 98 …”

Section: Epigenetic Regulation Of Circadian Rhythmsmentioning

confidence: 99%

Epigenetic regulation in obesity

2011

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The availability to the DNA strand and the activity of the transcription machinery is crucial for the cell to use the information in the DNA. The epigenetic mechanisms DNA methylation, modification of histone tails, other chromatin-modifying processes and interference by small RNAs regulate the cell-type-specific DNA expression. Epigenetic marks can be more or less plastic perpetuating responses to various molecular signals and environmental stimuli, but in addition apparently stochastic epigenetic marks have been found. There is substantial evidence from animal and man demonstrating that both transient and more long-term epigenetic mechanisms have a role in the regulation of the molecular events governing adipogenesis and glucose homeostasis. Intrauterine exposure such as poor maternal nutrition has consistently been demonstrated to contribute to a particular epigenotype and thereby developmental metabolic priming of the exposed offspring in animal and man. Epigenetic modifications can be passed not only from one cell generation to the next, but metabolic disease-related epigenotypes have been proposed to also be transmitted germ-line. Future more comprehensive knowledge on epigenetic regulation will complement genome sequence data for the understanding of the complex etiology of obesity and related disorder.

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Section: Epigenetic Regulation Of Circadian Rhythmsmentioning

confidence: 99%

Epigenetic regulation in obesity

2011

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“…During intrauterine life, the characteristics of the phenotype of an individual are formed [10]. Although the effect of the environment on phenotypic changes has not been sufficiently recognized, the opinion is uncontested that exposure of the foetus to hazardous agents transmitted by the organism of the mother induces changes in gene expression (epigenetic), which decide about predisposition of the organism to chronic diseases after birth and in adulthood [11].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy planning and risk behaviours – a survey of women’s experiences in selected European countries

Lesińska–Sawicka

Nagórska

2018

Ann Agric Environ Med.

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Lesińska-Sawicka M, Nagórska M. Pregnancy planning and risk behaviours -a survey of women's experiences in selected European countries. Ann Agric Environ Med. 2018; 25(1): 95-99. doi: 10.5604/12321966.1235162 Abstract Pregnancy, a special period in a woman's life, should be preceded by proper preparation: a positive attitude to procreation, selection of optimum time for becoming pregnant, starting prevention of neural tube defects, restriction of the use of drugs, smoking, etc. The aim of this study was to determine the effect of pregnancy planning and antenatal classes on the use of stimulants during pregnancy. The study group included 877 women living in 7 European countries, and their experiences of planning pregnancy and substance abuse during pregnancy were investigated. In about a half (50.3%) of respondents the pregnancy was planned. The highest percentage of mothers who planned pregnancy was recorded in Poland and Bulgaria (about 76%). By contrast, in Germany the proportion of mothers who planned pregnancy was the lowest (46.2%). Surprisingly, they became pregnant despite very frequent use of birth control (96.7%). On average, 17.3% of respondents disclosed that they drank alcohol or coffee, smoked cigarettes or used psychoactive drugs during pregnancy. Among women who did not plan to be pregnant, the use of stimulants was recorded more often. However, pregnancy planning only slightly inclined women to stop the consumption of stimulants. Attendance at antenatal classes did not have any significant effect on the use of stimulants.

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“…As discussed above, it is unclear whether this is the result of variation in genomic susceptibility, rendered maternal parent of origin effect 48 , or alternately a dominance of epigenomic modifications in key gene regulatory events. Given our prior observations regarding offspring epigenomic reprogramming and persistent intestinal dysbiosis (gut microbiome variation), it is intriguing to speculate on the potential relative effect size measures of such modifiable events 19,[24][25][26] . Based on these collective phenotypic and molecular observations in primates, we speculate that while there may be genomic-mediated variation in obese resistance to chronic high in a first generation (the dams), the same would not hold true for their offspring as a result of maternal diet-induced epigenomic and metagenomics modifications in the offspring.…”

Section: Discussionmentioning

confidence: 99%

“…To identify functional and potentially novel SNPs associated with sensitivity or resistance to the development of obesity with high fat diet consumption present in our well characterized Japanese macaque (Macaca fuscata) model [20][21][22][23][24][25][26][27][28][29][30][31][32][33] , we designed an exon capture array that enriches for targeted exonic segments with similarity to the array probes (Supplemental Fig. 1).…”

Section: Novel Snp Identification and Genotyping With An Exon-hybrid mentioning

confidence: 99%

“…To this end, we have spent nearly a decade establishing and characterizing the effect of obesity and chronic high fat dietary exposure on adult female dams and their offspring in Macaca fuscata (Japanese macaque) [18][19][20][21] . Specifically, we have demonstrated that a high fat diet (HFD) comprised of 36% calories from fat during gestation and lactation structures the offspring's epigenome, metabolome, and intestinal microbiome 18,19,[22][23][24][25][26][27] ; these molecular and metabolic perturbations are accompanied by persistent changes in offspring behavior and impairments in critical neural circuitry despite weaning to a healthy diet 28 . Of interest, we have consistently observed that HFD feeding for 1-5 years prior to pregnancy leads to insulin resistance and obesity in the majority, but not all, exposed dams 18,23,26,27,[29][30][31] .…”

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confidence: 99%

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124: Genomic variants associated with resistance to high fat diet induced obesity in a primate model

Pace

Alcott

Sullivan

et al. 2017

American Journal of Obstetrics and Gynecology

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Maternal obesity contributes to an increased risk of lifelong morbidity and mortality for both the mother and her offspring. In order to better understand the molecular mechanisms underlying these risks, we previously established and extensively characterized a primate model in Macaca fuscata (Japanese macaque). In prior studies we have demonstrated that a high fat, caloric dense maternal diet structures the offspring's epigenome, metabolome, and intestinal microbiome. During the course of this work we have consistently observed that a 36% fat diet leads to obesity in the majority, but not all, of exposed dams. In the current study, we sought to identify the genomic loci rendering resistance to obesity despite chronic consumption of a high fat diet in macaque dams. Through extensive phenotyping together with exon capture array and targeted resequencing, we identified three novel single nucleotide polymorphisms (SNPs), two in apolipoprotein B (APOB) and one in phospholipase A2 (PLA2G4A) that significantly associated with persistent weight stability and insulin sensitivity in lean macaques. By application of explicit orthogonal modeling (NOIA), we estimated the polygenic and interactive nature of these loci against multiple metabolic traits and their measures (i.e., serum LDL levels) which collectively render an obesity resistant phenotype in our adult female dams.Obesity results from a complex set of interactions between genetics and the environment, and links behavior, metabolism and early in life exposure modeling. In the last several decades, a global epidemic of increasing rates of obesity in humans has been well described but relatively poorly understood at a genomic level 1 . Obesity is known to be heritable, with the most recent in a wave of meta-analyses of body mass index (BMI) genomewide association studies (GWAS) estimating that 97 loci account for approximately 2.7% of BMI variation, and common variants account for up to 21% of BMI variation 2 . However, these loci only nominally predict obesity (defined as BMI ≥ 30 kg per m 2 ), as measured by an improved area under the receiver-operating characteristic curve from 0.576 to 0.601 in a model including age, sex, and four genotype-based principal components 2 . Similarly, GWAS meta-analysis focused on the waist-to-hip ratio (WHR) as a measure of body fat distribution identified 20 loci with female sexual dimorphism which were associated with WHR adjusted for BMI 3 . Notably, these loci generally mapped to genes expressed in mesenchymal derived tissues that are linked to fat distribution and central obesity. These studies are consistent with prior equally robust GWAS analyses, alongside family, twin and adoption studies, and collectively suggest that a wide range (e.g., 40-70%) of inter-individual variability in BMI may be attributed to genetic factors, with FTO and near-MC4R loci seeming to affect obesity-susceptibility

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Epigenomics: maternal high‐fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates

Cited by 128 publications

References 74 publications

Epigenetic regulation in obesity

Epigenetic regulation in obesity

Pregnancy planning and risk behaviours – a survey of women’s experiences in selected European countries

124: Genomic variants associated with resistance to high fat diet induced obesity in a primate model

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