224: Obesity programs neonatal metabolic syndrome

Abstract

Greater than 65% of US adults are overweight or obese representing an obesity epidemic. Offspring born to mothers with a high body mass index or in pregnancies complicated by gestational diabetes show increased obesity and diabetes risk in later life. As the prevalence of obesity among pregnant women continues to rise, increasing number of children are exposed to an 'obese intrauterine environment' during development. We thus investigated whether exposure to maternal obesity in prenatal and postnatal period programs the risk of obesity in the offspring. Rats were fed a high fat diet (HF; 60% k/cal) from 3 weeks of age, mated at 11 weeks, and maintained on a HF diet throughout pregnancy and lactation. A control group was fed laboratory chow (10% k/cal). At 1 day of age, litter size was standardized and blood collected from excess pups. All offspring were nursed by their own dams. At 3 weeks of age, male offspring underwent DEXA scan and were fasted overnight for blood samples. Pregnant HF dams were significantly heavier than controls at conception (301±9 vs 233±8 g). At birth, HF newborns had similar body weights as the Controls (7.4±0.2 vs 7.3±0.1 g) though decreased plasma leptin levels (2.1±0.5 vs 4.9±0.9 ng/ml). At 3 weeks of age, HF offspring exhibited accelerated growth, resulting in significantly increased body weight (175±4 vs 146±3 g) and percent body fat (12.6±1.2 vs 6.4±1.0 %) with decreased percent lean body mass (85.5±1.3 vs 91.6±1.0 %). Additionally, HF offspring exhibited increased fasting blood glucose (131±6 vs 96±7 mg/dl), and plasma leptin (3.9±0.5 vs 1.3±0.2 ng/ml) and triglyceride (103±12 vs 68±8 mg/dl) levels. Despite no differences in body weights at birth, offspring of obese dams exhibit remarkably increased body weight, adiposity and metabolic abnormalities. Thus, maternal obesity during critical periods of development may increase the susceptibility of the offspring to metabolic syndrome early in life.