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: 3.53). 02/2008; 294(2):R528-38. DOI: 10.1152/ajpregu.00316.2007
Source: PubMed

ABSTRACT 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, Jul 09, 2015
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    • "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. "
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    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 · 3.29 Impact Factor
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    • "In humans, this period of developmental plasticity most likely corresponds to the third trimester of pregnancy and may expand into postnatal life [8]. However, only very few rodent studies have specifically investigated the transgenerational effects of maternal pre-gravid obesity and during the gestational period [9] [10], although an impact on oocyte and early embryo development has been suggested [11] [12]. "
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    ABSTRACT: Vulnerability of the fetus upon maternal obesity can potentially occur during all developmental phases. We aimed at elaborating longer-term health outcomes of fetal overnutrition during the earliest stages of development. We utilized NMRI mice to induce pre-conceptional and gestational obesity and followed offspring outcomes in the absence of any postnatal obesogenic influences. Male adult offspring developed overweight, insulin resistance, hyperleptinemia, hyperuricemia and hepatic steatosis; all these features not being observed in females. Instead, those showed impaired fasting glucose and a reduced fat mass and adipocyte size. Influences of the interaction of maternal diet*sex concerned offspring genes involved in fatty liver disease, lipid droplet size regulation and fat mass expansion. These data suggest that a peri-conceptional obesogenic exposure is sufficient to shape offspring gene expression patterns and health outcomes in a sex- and organ-specific manner, indicating varying developmental vulnerabilities between sexes towards metabolic disease in response to maternal overnutrition.
    Biochimica et Biophysica Acta 11/2013; 1842(2). DOI:10.1016/j.bbadis.2013.11.021 · 4.66 Impact Factor
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    • "Many of these patterns have been ascribed to epigenetic modification of key genes that regulate energy metabolism. Such mechanisms have been and continue to be explored and validated in rodent models (Levin & Govek, 1998; Nathanielsz, Poston, & Taylor, 2007; Samuelsson et al., 2008; Shankar et al., 2008). Thus, new research focusing on the specific modifications of nucleosomal histones in chromatin and DNA is worthy of attention. "
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    Vitamins & Hormones 01/2013; 91:49-75. DOI:10.1016/B978-0-12-407766-9.00003-1 · 1.78 Impact Factor