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.

42 Reads
    • "(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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "In a separate experiment, lean and OB rat dams were allowed to carry pregnancies to term and give birth naturally (N ¼ 8 per group). On PND2, four males and four females from each litter were cross-fostered to surrogate dams that had been previously time-impregnated to give birth on the same day as the dams receiving infusion diets [1] [2] [6]. Surrogate dams were not cannulated and had ad libitum access to AIN-93G diets throughout. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unknown. Methods Using a rat maternal obesity model, we conducted transcriptomic profiling of the utero-placental compartments and fetal liver (FL) at dpc 18.5, in conjunction with analyses of mRNA expression of key thyroid hormone (TH) signaling genes in the placenta, fetus and weanling offspring. Results and Discussion Gene expression analysis of placenta and offspring revealed that each utero-placental compartment responds distinctly to maternal OB with changes in inflammatory signaling, lipid metabolism and hormone stimulus being the predominant effects. OB-induced alterations in 17 genes were confirmed by qPCR, including reductions in thyrotropin-releasing hormone (Trh) in JZ. We further characterized mRNA and protein expression of TH signaling regulators including deiodinases (Dio), TH receptors (Tr), and downstream targets (uncoupling proteins (Ucp)). A concerted down-regulation of multiple facets of thyroid hormone signaling in the JZ and FL was observed. JZ expression of thyroid hormone signaling components Trh, Dio2, Trα, and Ucp2 were negatively associated with maternal leptin. mRNA expression of TRH, TRβ and UCP1 were also decreased in term placenta from OB women. Finally, our studies identified persistent impairments in expression of TH related genes in tissues from offspring of obese dams. Conclusions The role of lower placental thyroid expression is worthy of further study as a possible pathway that leads to low energy metabolism and obesity in animals born to obese mothers.
    Placenta 10/2014; 35(12). DOI:10.1016/j.placenta.2014.09.015 · 2.71 Impact Factor
Show more