Predictive value of maternal bodyweight, postnatal weight gain and prenatal dexamethasone overexposure for the development of obesity in adult marmoset monkeys

In rats, adult bodyweight is modulated by the intrauterine environment as well as early postnatal nutritional conditions. Along with fetal glucocorticoid overexposure or postnatal overfeeding persistent increases of bodyweight, blood pressure, liver enzymes (PEPCK) and a decrease in glucose tolerance are observed. Moreover, there is also evidence for a resistance against satiety signals in distinct brain regions. Whether prenatal glucocorticoid overexposure promotes obesity in primates is still matter of debate. We therefore investigated in offspring of marmoset monkeys the effect of intrauterine overexposure with the synthetic glucocorticoid dexamathasone (DEX) either during early or late pregnancy on weight gain, blood pressure and biochemical measures in a two year follow-up study. Marmoset monkeys (Callithrix jacchus) are small (˜400g) non-endangered South American non-human primates. They are of increasing interest in biomedical research because they share many similarities with humans and are easy to handle and to breed under standardized laboratory housing conditions. Three groups of pregnant marmoset monkeys were treated orally for one week with vehicle (CON; N=10) or with dexamethasone (5mg/kg daily) during early (E-DEX; pregnancy day 42–48; N=10) or late pregnancy (L-DEX; pregnancy day 90–96; N=10), respectively. In male offspring (N=30 experimental animals in total) bodyweight was recorded in weekly to monthly intervals. Blood pressure was measured and blood samples were collected at 6, 12, 18 and 24 months of age. Triglycerides, HDL-cholesterol, total cholesterol, fasting glucose, glucose after an oral glucose load (OGTT) and HbA1c were determined. In newborns, weight did not differ between groups. During the first two months after birth L-DEX offspring gained significantly (p<0.02) more weight than E-DEX and CON. In adulthood bodyweight correlated directly with maternal non-pregnant bodyweight (p<0.05) and the weight gain during two months after birth (p=0.01). Metabolic parameters and blood pressure correlated significantly (p<0.005) with bodyweight (negative correlation for HDL-cholesterol, positive correlation for all other parameters). As a consequence, offspring that showed rapid early weight gain and had an obese mother were likely to develop obesity with symptoms of metabolic syndrome, i.e. increased blood pressure, triglycerides, total cholesterol, fasting glucose, HbA1c and decreased HDL-cholesterol. Epidemiological studies in humans are consistent with these results showing that an obese mother and rapid early weight gain are risk factors for the development of obesity in later life. In contrast to the findings in rats, prenatal DEX overexposure seems to play a less important role for bodyweight development in marmosets. Due to the similarities to humans the marmoset monkey seems to be an ideal model for further studies on the regulation of early postnatal weight gain and its role for the development of metabolic disorders in adulthood. Supported by a European Commission Grant (QLRI-CT-2002–02758, EUPEAH).