Article

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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    • "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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    • "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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    • "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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