Fall CH. Evidence for the intra-uterine programming of adiposity in later life. Ann Hum Biol. 2011;38(4):410-28

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
Annals of Human Biology (Impact Factor: 1.27). 07/2011; 38(4):410-28. DOI: 10.3109/03014460.2011.592513
Source: PubMed


AIM: Research in animals has shown that altering foetal nutrition by under-nourishing or over-nourishing the mother or rendering her diabetic or foetal exposure to glucocorticoids and toxins can programme obesity in later life. The increased adiposity is mediated by permanent changes in appetite, food choices, physical activity and energy metabolism. In humans, increased adiposity has been shown in people who experienced foetal under-nutrition due to maternal famine or over-nutrition due to maternal diabetes. Lower birth weight (a proxy for foetal under-nutrition) is associated with a reduced adult lean mass and increased intra-abdominal fat. Higher birth-weight caused by maternal diabetes is associated with increased total fat mass and obesity in later life. There is growing evidence that maternal obesity, without diabetes, is also a risk factor for obesity in the child, due to foetal over-nutrition effects. Maternal smoking is associated with an increased risk of obesity in the children, although a causal link has not been proven. Other foetal exposures associated with increased adiposity in animals include glucocorticoids and endocrine disruptors. CONCLUSIONS: Reversing the current obesity epidemic will require greater attention to, and better understanding of, these inter-generational (mother-offspring) factors that programme body composition during early development.

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    • "In the pig, nutrient defi ciencies early in pregnancy that compromise placental development permanently reprogram myogenesis, with lasting consequences for growth potential and carcass quality (Foxcroft et al., 2006), and in beef cattle, undernutrition of ~75% of recommended allowance during early stages of pregnancy compromises placental angiogenesis, cotyledon weight, and thus, fetal development (Vonnahme et al., 2007; Long et al., 2009). Increased adiposity of the fetus seems to be among the potential negative outcomes of an inadequate placental development in humans (Fall, 2011) and sheep (Bispham et al., 2003; Ford et al., 2007). Unfortunately, no information is available for dairy cattle, and there exists a strong need to evaluate this aspect because fat reserves and mobilization play an important role in early lactation. "
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    • "More than 60% of all adults are classified as overweight or obese in most westernized societies, and as the prevalence of obesity increases it is responsible for an ever larger proportion of the overall burden of disease (Nguyen and El-Serag 2010; Ng et al. 2014). It has been well documented that maternal obesity predisposes offspring to obesity, independently of genetic inheritance (Fall 2011), thus providing the potential for intergenerational amplification of obesity and its comorbidities (Dunn and Bale 2009, 2011). Rodent models of diet-induced obesity with or without altered glucose homeostasis in the father have also been shown to impair the metabolic and reproductive health of both male and female offspring via nongenetic pathways (Ng et al. 2010; Fullston et al. 2012, 2013). "
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    ABSTRACT: Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic and reproductive health of male offspring, despite their control diet (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if male offspring from HFD fathers have a heightened susceptibility to HFD-induced metabolic and reproductive derangements. This 2 × 2 design saw founder males (F0) and their offspring (F1) fed either a HFD or a nutritionally matched CD. Regardless of paternal diet, HFD fed male offspring had greater total body weight and adiposity. Offspring sired by a HFD male and fed a HFD were the heaviest, had the greatest adiposity and had the greatest concentration of serum cholesterol, triglyceride, HDL, and NEFA compared with CD sired/fed littermates. A synergistic increase in serum insulin was unmasked by both father/son HFD consumption, concomitant with increased sera glucose. Either a paternal or offspring HFD was associated with similar reductions to offspring sperm motility. Whereas sperm ROS concentrations and sperm-oocyte binding saw detrimental effects of both F0 HFD and F1 HFD with an interaction evident between both, culminating in the most impaired sperm parameters in this group. This indicates that metabolic and fertility disturbances in male offspring sired by HFD fathers are exacerbated by a "second-hit" of exposure to the same obesogenic environment postnatally. If translatable to human health, this suggests that adverse reproductive and metabolic outcomes may be amplified across generations through a shared calorie dense diet, relevant to the current worldwide obesity epidemic. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    03/2015; 3(3). DOI:10.14814/phy2.12336
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    • "Lots of studies have shown that maternal hyperglycemia during pregnancy is associated with increased risk of specific maternal-fetal complications, including pregnancy induced hypertension (PIH), preeclampsia, cesarean section, stillbirth, congenital defects, neonatal hypoglycemia and neonatal hyperbilirubinemia [3-5]. In the long term, for the mothers, there is an increased risk for developing Type 2 diabetes mellitus (T2DM) after pregnancy [2,6]; for the offspring, studies have provided substantial evidences that intrauterine exposure to maternal hyperglycemia has lifelong effects, including increased risk of obesity [7,8], T2DM [9,10], metabolic [11-14] and cardiovascular disease [15,16] and even cancer [17]. These hyperglycemia-related short or long term dysfunctions are not only confined to women with Type 1 diabetes mellitus (T1DM) or T2DM diagnosed before gestation, but are also observed in women with GDM. "
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    ABSTRACT: The purposes of this study were to explore whether the maternal-fetal outcomes differed among various types of hyperglycemia during pregnancy and whether the values of glycemic screening in the middle phase of pregnancy could predict maternal-fetal outcomes. A retrospective study was conducted to study the incidence of maternal-fetal outcomes in 383 singleton pregnant women with diabetes or gestational diabetes admitted to our hospital from November 2007 to March 2013. Patients were divided into three groups: DM (Type 1 and Type 2 diabetes mellitus) group, mGDM (mild gestational diabetes mellitus) group and sGDM (severe gestational diabetes mellitus) group. Maternal basic characteristics, results of oral glucose tolerance test (OGTT), antenatal random glycemia and maternal-fetal outcomes were collected. Binary logistic regression was used to estimate the association of blood glucose with the maternal-fetal outcomes. Predictive accuracy was assessed by calculating the areas under the receiver operating characteristic curves. The maternal basic characteristics, maternal complications and neonatal complications did not differ significantly between DM group and sGDM group, except neonatal intensive care units admission (NICU). Incidences of preterm, NICU and preeclampsia were significantly lower in the mGDM group than in the DM and sGDM groups (P < 0.05). After adjusted by confounding factors, the value of OGTT 0 h could predict pregnancy induced hypertension (PIH) (OR = 1.24, 95%CI [1.04 to 1.46], P = 0.015), preterm birth (OR = 1.23, 95%CI [1.03 to 1.47], P = 0.025) and stillbirth (OR = 1.55, 95%CI [1.14 to 2.10], P = 0.005); antenatal random glycemia could predict preterm birth (OR = 1.19, 95%CI [1.08 to 1.31], P < 0.001) and stillbirth (OR = 1.41, 95%CI [1.17 to 1.71], P < 0.001). Pregnant women in the mGDM group have better outcomes than those in the DM and sGDM groups. The values of OGTT in the middle phase of pregnancy and antenatal random glycemia could predict PIH, preterm birth or stillbirth to some extent.
    BMC Pregnancy and Childbirth 01/2014; 14(1):34. DOI:10.1186/1471-2393-14-34 · 2.19 Impact Factor
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