Clinical Nutrition Center, Xin Hua Hospital, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, People's Republic of China.
J Mol Endocrinol. 2012 Jul 25;49(2):107-14. doi: 10.1530/JME-12-0046. Print 2012 Oct.
Maternal high-fat (HF) diets during gestation and lactation have been shown to contribute to metabolic disorders in offspring. Molecular and epigenetic mechanisms underlying this connection may be essential for the prevention and treatment of the fetal origins of metabolic diseases. The current study examined the impact of maternal HF diets on Wnt signaling and histone modification in offspring. Time-pregnant Sprague-Dawley rats were fed either control diet or HF diet during gestation and lactation and then the neonatal offspring of both groups were investigated. The neonatal offspring born to dams fed on HF diets exhibited increases in serum glucose and liver triglyceride levels. Maternal exposure to the HF diet also repressed the mRNA expression of Wnt1 and nuclear β-catenin protein in the liver of offspring. The altered Wnt1 gene expression may be due to the changes of acetylation of H4 at its promoter as well as acetylation of H4 and methylation of H3K9 at coding region. Maternal exposure to the HF diet induced suppression of the Wnt/β-catenin signaling pathway through histone modification, potentially increasing the risk of metabolic syndrome.
母体高脂肪（HF）饮食在妊娠和哺乳期已被证明会导致后代代谢紊乱。这种联系的分子和表观遗传机制对于预防和治疗代谢疾病的胎儿起源可能至关重要。本研究探讨了母体 HF 饮食对后代 Wnt 信号和组蛋白修饰的影响。妊娠期间，时间怀孕的 Sprague-Dawley 大鼠分别喂食对照饮食或 HF 饮食，然后对两组的新生后代进行研究。喂食 HF 饮食的母鼠所生的新生后代血清葡萄糖和肝甘油三酯水平升高。母体暴露于 HF 饮食还抑制了后代肝脏中 Wnt1 和核 β-连环蛋白蛋白的 mRNA 表达。Wnt1 基因表达的改变可能是由于其启动子处 H4 的乙酰化以及编码区处 H4 的乙酰化和 H3K9 的甲基化的变化所致。母体暴露于 HF 饮食通过组蛋白修饰诱导 Wnt/β-连环蛋白信号通路的抑制，可能会增加代谢综合征的风险。
