Burdge Graham C, Lillycrop Karen A, Phillips Emma S, Slater-Jefferies Joanne L, Jackson Alan A, Hanson Mark A
Institute of Human Nutrition.
J Nutr. 2009 Jun;139(6):1054-60. doi: 10.3945/jn.109.104653. Epub 2009 Apr 1.
Prenatal nutritional constraint is associated with increased risk of metabolic dysregulation in adulthood contingent on adult diet. In rats, folic acid supplementation of a protein-restricted (PR) diet during pregnancy prevents altered phenotype and epigenotype in the offspring induced by the PR diet. We hypothesized that increasing folic acid intake during the juvenile-pubertal (JP) period would reverse the effects of a maternal PR diet on the offspring. Rats were fed a control (C) or PR diet during pregnancy and AIN93G during lactation. Offspring were weaned on d 28 onto diets containing 1 mg [adequate folate (AF)] or 5 mg [folic acid-supplemented (FS)] folic acid/kg feed. After 28 d, all offspring were fed a high-fat (18% wt:wt) diet and killed on d 84. As expected, offspring of PR dams fed the AF diet had increased fasting plasma triglyceride (TAG) and beta-hydroxybutyrate (betaHB) concentrations. The FS diet induced increased weight gain, a lower plasma betaHB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPARalpha and glucocorticoid receptor promoter methylation increased in liver and insulin receptor promoter methylation decreased in liver and adipose tissue in FS compared with AF offspring, with reciprocal changes in mRNA expression irrespective of maternal diet. These findings show that increased folic acid intake during the JP period did not simply reverse the phenotype induced by the maternal diet. This may represent a period of plasticity when specific nutrient intakes may alter the phenotype of the offspring through epigenetic changes in specific genes.
产前营养限制与成年期代谢失调风险增加有关，这取决于成年期饮食。在大鼠中，孕期蛋白质限制（PR）饮食补充叶酸可预防PR饮食诱导的后代表型和表观基因型改变。我们假设在青少年-青春期（JP）期间增加叶酸摄入量可逆转母体PR饮食对后代的影响。大鼠在孕期喂食对照（C）或PR饮食，哺乳期喂食AIN93G。后代在第28天断奶，改喂含1毫克[充足叶酸（AF）]或5毫克[叶酸补充（FS）]叶酸/千克饲料的饮食。28天后，所有后代均喂食高脂（18%重量：重量）饮食，并在第84天处死。正如预期的那样，喂食AF饮食的PR母鼠后代空腹血浆甘油三酯（TAG）和β-羟基丁酸（βHB）浓度升高。与AF后代相比，无论母体饮食如何，FS饮食均导致体重增加、血浆βHB浓度降低、肝脏和血浆TAG浓度升高。与AF后代相比，FS后代肝脏中PPARα和糖皮质激素受体启动子甲基化增加，肝脏和脂肪组织中胰岛素受体启动子甲基化降低，且mRNA表达发生相反变化，与母体饮食无关。这些发现表明，JP期间叶酸摄入量增加并不能简单地逆转母体饮食诱导的表型。这可能代表了一个可塑性时期，特定的营养摄入可能通过特定基因的表观遗传变化改变后代的表型。
