Maternal obesity at conception programs obesity in the offspring

Arkansas Children's Nutrition Center, 1212 Marshall Street, Little Rock, AR 72202, USA.
AJP Regulatory Integrative and Comparative Physiology (Impact Factor: 3.11). 02/2008; 294(2):R528-38. DOI: 10.1152/ajpregu.00316.2007
Source: PubMed


Risk of obesity in adult life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in offspring, we developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via total enteral nutrition. Feeding liquid diets to adult female rats at 220 kcal/kg(3/4) per day (15% excess calories/day) compared with 187 kcal/kg(3/4) per day for 3 wk caused substantial increase in body weight gain, adiposity, serum insulin, leptin, and insulin resistance. Lean or obese female rats were mated with ad libitum AIN-93G-fed male rats. Exposure to obesity was ensured to be limited only to the maternal in utero environment by cross-fostering pups to lean dams having ad libitum access to AIN-93G diets throughout lactation. Numbers of pups, birth weight, and size were not affected by maternal obesity. Male offspring from each group were weaned at postnatal day (PND)21 to either AIN-93G diets or high-fat diets (45% fat calories). Body weights of offspring from obese dams did not differ from offspring of lean dams when fed AIN-93G diets through PND130. However, offspring from obese dams gained remarkably greater (P < 0.005) body weight and higher % body fat when fed a high-fat diet. Body composition was assessed by NMR, X-ray computerized tomography, and weights of adipose tissues. Adipose histomorphometry, insulin sensitivity, and food intake were also assessed in the offspring. Our data suggest that maternal obesity at conception leads to fetal programming of offspring, which could result in obesity in later life.

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Available from: Kartik Shankar,
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    • "Subcutaneous adipocyte hypertrophy is closely linked with obesity (Shankar et al., 2008; O'Connell et al., 2010) and is a postnatal phenotypic consequence of in utero undernutrition (Nguyen et al., 2010; García et al., 2011). In the present study, subcutaneous adipocyte size was increased (87%) in IUPFTN compared to IUHS and IUTN progeny (Table 4; Fig. 5). "
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    ABSTRACT: We recently demonstrated that in utero heat stress (IUHS) alters future tissue accretion in pigs, but whether this is a conserved response among species, is due to the direct effects of heat stress (HS) or mediated by reduced maternal feed intake (FI) is not clear. Study objectives were to compare the quantity and rate of tissue accretion in rats exposed to differing in utero thermal environments while eliminating the confounding effect of dissimilar maternal FI. On d3 of gestation, pregnant Sprague Dawley rats (189.0 ± 5.9 g BW) were exposed to thermoneutral (TN; 22.2 ± 0.1°C; n=8), or HS conditions (cyclical 30 to 34oC; n=8) until d18 of gestation. A third group was pair-fed to HS dams in TN conditions (PFTN; 22.2 ± 0.1°C; n=8) from d4 to d19 of gestation. HS increased dam rectal temperature (p=0.01; 1.3oC) compared to TN and PFTN mothers, and reduced FI (p=0.01; 33%) compared to TN ad libitum fed controls. Although litter size was similar (p=0.97; 10.9 pups/litter), pup birth weight was reduced (p = 0.03; 15.4%) in HS compared to PFTN and TN dams. Two male pups per dam [n=8 in utero TN (IUTN); n=8 IUHS; n=8 in utero PFTN (IUPFTN)] were selected from four dams per treatment based on similar gestation length, and body composition was determined using dual-energy x-ray absorptiometry (DXA) on d26, d46, and d66 of postnatal life. Whole- body fat content increased (p=0.01; 11.2%), and whole-body lean tissue decreased (p=0.01; 2.6%) in IUPFTN versus IUTN and IUHS offspring. Whole-body composition was similar between IUHS and IUTN offspring. Epididymal fat pad weight increased (p=0.03; 21.6%) in IUPFTN versus IUHS offspring. In summary and in contrast to pigs, IUHS did not impact rodent body composition during this stage of growth; however, IUPFTN altered the future hierarchy of tissue accretion.
    Journal of Thermal Biology 10/2015; 53:143-150. DOI:10.1016/j.jtherbio.2015.10.002 · 1.51 Impact Factor
    • "(2015), Animal models have revealed mechanisms underlying programming by maternal obesity Animal studies have confirmed that maternal obesity programs metabolic syndrome—like outcomes in the offspring including impaired insulin action and glucose homeostasis (Martin-Gronert et al., 2010; Samuelsson et al., 2008; Shankar et al., 2010; Shelley et al., 2009), hypertension, and cardiovascular dysfunction (Blackmore et al., 2014; Fernandez-Twinn et al., 2012; Samuelsson et al., 2008), as well as increased adiposity (Bayol et al., 2008; Samuelsson et al., 2008; Song et al., 2015), and an increased susceptibility to diet-induced obesity (DIO) (Bayol et al., 2007; Howie et al., 2009; Kirk et al., 2009; Nivoit et al., 2009; Samuelsson et al., 2008; Shankar et al., 2008; Torrens et al., 2012). The choice of animal model is often a compromise between practicality of the research and translatability to humans. "
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    ABSTRACT: Obesity in women of child-bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models. Copyright © 2015. Published by Elsevier Inc.
    Hormones and Behavior 07/2015; DOI:10.1016/j.yhbeh.2015.06.015 · 4.63 Impact Factor
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    • "Several physiological and metabolic mechanisms are not fully matured at birth and continue maturation in the immediate postnatal period, for example, neurons and pancreatic islets continue to develop after birth in rodents [41]. Many studies have exposed female animals for a high fat diet early in life; during pregnancy or during lactation, or during both periods, and found long-term consequences of metabolic and endocrine pathophysiology in one or both genders of the offspring as adults, both in mice [42] [43] [44] and rats [45] [46] [47] [48]. Interestingly, prenatal stress seems to have similar effects as a high fat diet for increased susceptibility to diet-induced obesity in the offspring [47]. "
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    ABSTRACT: We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min (multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat diet in utero, during nursing, during both in utero and nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during both in utero and nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat diet in utero, during nursing, or during both in utero and nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or during in utero and nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.
    Journal of obesity 04/2015; 2015:624023. DOI:10.1155/2015/624023
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