Folic Acid Supplementation during the Juvenile-Pubertal Period in Rats Modifies the Phenotype and Epigenotype Induced by Prenatal Nutrition
Folic Acid Supplementation during the Juvenile-Pubertal Period in Rats Modifies the Phenotype and Epigenotype Induced by Prenatal Nutrition
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DOI：
10.3945/jn.109.104653
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发表时间：
2009-06-01
影响因子：
4.2
通讯作者：
Hanson, Mark A.
中科院分区：
文献类型：
--
作者：
Burdge, Graham C.;Lillycrop, Karen A.;Hanson, Mark A.
产前营养限制与成年期代谢失调风险增加有关，取决于成人饮食。在大鼠中，叶酸补充蛋白质限制（PR）饮食在怀孕期间防止改变表型和表观基因型的后代诱导的PR饮食。我们假设在青少年-青春期增加叶酸摄入量将逆转母体PR饮食对后代的影响。大鼠在妊娠期间喂食对照（C）或PR饮食，在哺乳期间喂食AIN 93 G。后代断奶的第28天，饮食含有1毫克[足够的叶酸（AF）]或5毫克[叶酸补充（FS）]叶酸/公斤饲料。28 cl后，所有后代喂食高脂肪（18%wt：wt）饮食，并在第84天处死。正如预期的那样，饲喂AF饲料的PR母鼠的后代空腹血浆甘油三酯（TAG）和β-羟基丁酸酯（β HB）浓度升高。与AF后代相比，FS饮食诱导体重增加，血浆β HB浓度降低，肝脏和血浆TAG浓度升高，与母体饮食无关。与AF后代相比，FS中肝脏和脂肪组织中的PPAR α和糖皮质激素受体启动子甲基化增加，胰岛素受体启动子甲基化降低，mRNA表达的相互变化与母体饮食无关。这些发现表明，在JP期间增加叶酸摄入量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，特定的营养摄入量可能会通过特定基因的表观遗传变化改变后代的表型。J.营养139：1054-1060，2009.
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 UP) 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 cl, 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 (beta HB) concentrations. The FS diet induced increased weight gain, a lower plasma beta HB concentration, and increased hepatic and plasma TAG concentration compared with AF offspring irrespective of maternal diet. PPAR alpha 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. J. Nutr. 139: 1054-1060, 2009.