The Sansom Institute of Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 50000, Australia.
Prog Biophys Mol Biol. 2011 Jul;106(1):307-14. doi: 10.1016/j.pbiomolbio.2010.12.004. Epub 2010 Dec 17.
Women entering pregnancy with a high body weight and fat mass have babies at increased risk of becoming overweight or obese in childhood and later life. It is not known, whether exposure to a high level of maternal nutrition before pregnancy and exposure to a high transplacental nutrient supply in later pregnancy act through similar mechanisms to program later obesity. Using the pregnant sheep we have shown that maternal overnutrition in late pregnancy results in an upregulation of PPARγ activated genes in fetal visceral fat and a subsequent increase in the mass of subcutaneous fat in the postnatal lamb. Exposure to maternal overnutrition during the periconceptional period alone, however, results in an increase in total body fat mass in female lambs only with a dominant effect on visceral fat depots. Thus the early programming of later obesity may result from 'two hits', the first occurring as a result of maternal overnutrition during the periconceptional period and the second occurring as a result of increased fetal nutrition in late pregnancy. Whilst a short period of dietary restriction during the periconceptional period reverses the impact of periconceptional overnutrition on the programming of obesity, it also results in an increased lamb adrenal weight and cortisol stress response, together with changes in the epigenetic state of the insulin like growth factor 2 (IGF2) gene in the adrenal. Thus, not all of the effects of dietary restriction in overweight or obese mother in the periconceptional period may be beneficial in the longer term.
体重和脂肪含量较高的女性在怀孕期间，其婴儿在儿童期和以后的生活中超重或肥胖的风险增加。目前尚不清楚妊娠前暴露于高水平的母体营养和妊娠后期暴露于高胎盘营养供应是否通过类似的机制来编程以后的肥胖。使用怀孕的绵羊，我们已经表明，妊娠晚期母体营养过剩会导致胎儿内脏脂肪中 PPARγ 激活基因的上调，并随后导致产后羔羊皮下脂肪质量的增加。然而，仅在围孕期暴露于母体营养过剩会导致雌性羔羊的总体脂肪质量增加，对内脏脂肪的影响占主导地位。因此，后期肥胖的早期编程可能是由“双重打击”引起的，第一次是由于围孕期母体营养过剩，第二次是由于妊娠后期胎儿营养增加。虽然在围孕期进行短期饮食限制可以逆转围孕期营养过剩对肥胖编程的影响，但它也会导致羔羊肾上腺重量增加和皮质醇应激反应增加，以及肾上腺中胰岛素样生长因子 2 (IGF2) 基因的表观遗传状态发生变化。因此，在围孕期超重或肥胖的母亲进行饮食限制的并非所有影响在长期内都是有益的。
