School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK.
Br J Nutr. 2012 Apr;107(7):964-78. doi: 10.1017/S0007114511003916. Epub 2011 Aug 24.
In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.
除了是妊娠不良结局的一个风险因素外，母体肥胖可能在决定后代长期疾病模式方面发挥作用，代谢和饮食因素直接影响胎儿发育。本研究评估了在妊娠前、妊娠期间、哺乳期以及断乳后给大鼠喂食致肥胖的自助餐厅饮食 (O) 的可能性，以编程葡萄糖耐量。 早期生命中接触 O 饮食对后代的食物摄入量没有显著影响。 与 O 喂养相关的早期生命编程导致母体肥胖与断奶后代的脂肪减少有关。 早期生命暴露于 O 饮食并在低脂肪饲料上断奶的成年后代具有较低的空腹血糖和胰岛素浓度，并且在腹腔内葡萄糖耐量试验期间似乎对胰岛素更敏感。 当在 O 饮食上断奶时，雄性后代比雌性后代更容易出现葡萄糖不耐受。 基于血糖曲线下面积，从交配前到哺乳期的任何时间的母体 O 喂养均与葡萄糖耐量受损相关。 虽然没有确定这种机制，但 Akt2 的肝表达增加可能表明胰岛素信号通路受到干扰。 本研究的观察结果证实，妊娠期间母体营养过剩和肥胖是后代代谢紊乱的危险因素。 尽管对葡萄糖稳态的影响与后代的肥胖无关，但仅当后代在诱导更多脂肪沉积的饮食上断奶时，才观察到不耐受葡萄糖的表型编程。
