Zhang Junlong, Zhang Fang, Didelot Xavier, Bruce Kimberley D, Cagampang Felino R, Vatish Manu, Hanson Mark, Lehnert Hendrik, Ceriello Antonio, Byrne Christopher D
Clinical Science Research Institute, Warwick Medical School, Clinical Sciences Building, University Hospital, Walsgrave Campus, Coventry, UK.
BMC Genomics. 2009 Oct 16;10:478. doi: 10.1186/1471-2164-10-478.
miRNAs play important roles in the regulation of gene functions. Maternal dietary modifications during pregnancy and gestation have long-term effects on the offspring, but it is not known whether a maternal high fat (HF) diet during pregnancy and lactation alters expression of key miRNAs in the offspring.
We studied the effects of maternal HF diet on the adult offspring by feeding mice with either a HF or a chow diet prior to conception, during pregnancy and lactation, and all offspring were weaned onto the same chow diet until adulthood. Maternal HF fed offspring had markedly increased hepatic mRNA levels of peroxisome proliferator activated receptor-alpha (ppar-alpha) and carnitine palmitoyl transferase-1a (cpt-1a) as well as insulin like growth factor-2 (Igf2). A HF diet induced up-regulation of ppar-alpha and cpt-1a expression in the wild type but not in Igf2 knock out mice. Furthermore, hepatic expression of let-7c was also reduced in maternal HF fed offspring. Among 579 miRNAs measured with microarray, ~23 miRNA levels were reduced by ~1.5-4.9-fold. Reduced expression of miR-709 (a highly expressed miRNA), miR-122, miR-192, miR-194, miR-26a, let-7a, let7b and let-7c, miR-494 and miR-483* (reduced by ~4.9 fold) was validated by qPCR. We found that methyl-CpG binding protein 2 was the common predicted target for miR-709, miR-let7s, miR-122, miR-194 and miR-26a using our own purpose-built computer program.
Maternal HF feeding during pregnancy and lactation induced co-ordinated and long-lasting changes in expression of Igf2, fat metabolic genes and several important miRNAs in the offspring.
微小RNA（miRNAs）在基因功能调控中发挥重要作用。孕期和哺乳期母体饮食的改变会对后代产生长期影响，但孕期和哺乳期母体高脂（HF）饮食是否会改变后代关键miRNAs的表达尚不清楚。
我们通过在受孕前、孕期和哺乳期给小鼠喂食高脂或正常饮食，研究了母体高脂饮食对成年后代的影响，所有后代断奶后均喂食相同的正常饮食直至成年。母体高脂饮食喂养的后代肝脏中过氧化物酶体增殖物激活受体α（ppar-α）、肉碱棕榈酰转移酶-1a（cpt-1a）以及胰岛素样生长因子2（Igf2）的mRNA水平显著升高。高脂饮食诱导野生型小鼠中ppar-α和cpt-1a表达上调，但在Igf2基因敲除小鼠中未出现这种情况。此外，母体高脂饮食喂养的后代肝脏中let-7c的表达也降低。在通过微阵列检测的579种miRNAs中，约23种miRNA水平降低了约1.5至4.9倍。通过定量聚合酶链反应（qPCR）验证了miR-709（一种高表达的miRNA）、miR-122、miR-192、miR-194、miR-26a、let-7a、let7b和let-7c、miR-494以及miR-483*（降低约4.9倍）的表达降低。使用我们自己专门编写的计算机程序，我们发现甲基化CpG结合蛋白2是miR-709、miR-let7s、miR-122、miR-194和miR-26a的共同预测靶点。
孕期和哺乳期母体高脂喂养会导致后代中Igf2、脂肪代谢基因以及几种重要miRNAs的表达发生协同且持久的变化。
