Effects of Maternal Surgical Weight Loss in Mothers on Intergenerational Transmission of Obesity

Smith, Jessica; Cianflone, Katherine; Biron, Simon; Hould, Frédéric‐Simon; Lebel, Stéfane; Marceau, Simon; Lescelleur, Odette; Biertho, Laurent; Simard, Serge; Kral, John G.; Marceau, Picard

doi:10.1097/ogx.0b013e3181e39cbf

Cited by 79 publications

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“…In conclusion, our study as well as others has demonstrated health benefits for offspring after maternal bypass surgery (20,35). We demonstrate unique altered methylation and gene expression profiles, comparing offspring born before to those born after maternal bypass surgery.…”

Section: Discussionmentioning

confidence: 80%

“…Several studies have demonstrated changes in genes associated with insulin action after bariatric operations (17,18). In previous studies, we demonstrated that the prevalence of obesity in children born after maternal bypass surgery (AMS) was significantly lower than in siblings born before maternal surgery (BMS) (19) and was associated with greater insulin sensitivity, less adiposity, hypertension, and dyslipidemia compared with BMS offspring, suggesting that these improvements in cardiometabolic markers may be attributable to an improved intrauterine environment (20).…”

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confidence: 99%

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Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery

Guénard¹,

Deshaies

Cianflone

et al. 2013

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

198

153

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Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.developmental origins | epigenetics | intrauterine environment | glucose metabolism | adiposity C hildhood overweight and obesity have increased dramatically in recent decades (1). Parental obesity increases the risk of obesity in offspring through genetic, biological, and environmental influences evident in associations between maternal body mass index (BMI), offspring adiposity, and cardiovascular disease (CVD) risk factors (2-4). Maternal obesity, weight gain, increased interpregnancy BMI, and gestational diabetes all increase risks of offspring obesity and type 2 diabetes mellitus (T2DM) (5, 6). Several genetic studies of nutritional response and metabolic control support the hypothesis that specific epigenetic changes contribute to early nutritional fetal programming, increasing the risk of metabolic disorders later in life (7-9).The intrauterine environment including nutritional factors, toxic exposures, and maternal stress participates in fetal programming (10). Maternal diet and adiposity impact methylation levels affecting specific gene functions. Prenatal exposure to famine during the Dutch hunger winter of 1944 is associated with obesity with less DNA methylation ("undermethylation") of the imprinted insulin-like growth factor 2 (IGF2) gene in exposed offspring relative to their unexposed siblings (11). Recently, retinoid X receptor alpha (RXRA) promoter methylation was demonstrated to correlate with increased adiposity in two independent cohorts of ch...

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Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery

Guénard¹,

Deshaies

Cianflone

et al. 2013

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

198

153

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“…Reproductive age women are also of particular interest because of the link among maternal obesity, gestational diabetes, adverse perinatal outcomes, and transgenerational transmission of a metabolic phenotype to the offspring. Despite previous concerns about the potentially deleterious effect of bariatric surgery on maternal nutrition, bariatric surgery has been demonstrated to improve maternal outcomes and likely improves neonatal outcomes [11,12]. Although women disproportionately undergo bariatric surgery, the rodent models investigating the mechanisms of bariatric surgery have been limited to males.…”

Section: Discussionmentioning

confidence: 99%

Hematological, Biochemical, and Immunological Laboratory and Histomorphological Effects of Sleeve Gastrectomy on Female Rats

et al. 2013

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Restriction of food intake leads to immunologic and histomorphological changes in rats demonstrated by Moriyama. This study is planned to show how sleeve gastrectomy restricts food intake and its effects on biochemical liver function, immunologic and hematologic laboratory parameters, and histomorphological changes in rats. We used sleeve gastrectomy model on seven young adult female rats and compared study group with sham and control groups. Food consumption of rats was measured. All rats were sacrificed on the 50th day, and blood and tissue samples were collected. There was a significant low food intake in sleeve gastrectomy group (p=0.013). No differences were observed on hematologic, biochemical, and immunologic laboratory parameters between groups. Toxicity parameters in liver samples such as cytoplasmic atrophy, single-cell hepatocellular necrosis, and necrotic eosinophilic cells were significantly high in sleeve gastrectomy group (p=0.005). Histomorphological examination of the spleen and kidneys revealed significant changes in sleeve gastrectomy and sham groups compared with controls (p=0.004 and p=0.018, respectively). Although sleeve gastrectomy does not lead to alteration in hematologic, biochemical, and immunologic laboratory parameters, it causes decreased food consumption, which results in toxicological histomorphological changes in rat liver as well as some changes in kidney and spleen samples.

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“…A follow-up study of 111 children from 49 obese mothers who had lost 36G1.8% body weight sustained for 12G0.8 years with bariatric surgery (weight loss surgery) showed that the children had lower birth weight associated with reduced prevalence of macrosomia. At follow-up at the age of 2.5-26 years, the children were leaner, and had improved metabolic profiles with greater insulin sensitivity and improved lipid profile (Smith et al 2009a). However, there remain many questions, including when is the best time for women to lose weight when planning pregnancy, and how should they manage their weight when pregnant?…”

Section: Other Programming Targetsmentioning

confidence: 99%

Impact of maternal obesity on offspring obesity and cardiometabolic disease risk

Drake¹,

Reynolds²

2010

Reproduction

442

308

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The prevalence of obesity among pregnant women is increasing. In addition to the short-term complications of obesity during pregnancy in both mother and child, it is now recognised that maternal obesity has long-term adverse outcomes for the health of her offspring in later life. Evidence from both animal and human studies indicates that maternal obesity increases the risk for the offspring in developing obesity and altering body composition in child-and adulthood and, additionally, it also has an impact on the offspring's cardiometabolic health with dysregulation of metabolism including glucose/insulin homoeostasis, and development of hypertension and vascular dysfunction. Potential mechanisms include effects on the development and function of adipose tissue, pancreas, muscle, liver, the vasculature and the brain. Further studies are required to elucidate the mechanisms underpinning the programming of disease risk in the offspring as a consequence of maternal obesity. The ultimate aim is to identify potential targets, which may be amenable to prevention or early intervention in order to improve the health of this and future generations.

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Effects of Maternal Surgical Weight Loss in Mothers on Intergenerational Transmission of Obesity

Cited by 79 publications

References 0 publications

Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery

Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery

Hematological, Biochemical, and Immunological Laboratory and Histomorphological Effects of Sleeve Gastrectomy on Female Rats

Impact of maternal obesity on offspring obesity and cardiometabolic disease risk

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