DNA hypomethylation of inflammation-associated genes in adipose tissue of female mice after multigenerational high fat diet feeding
DNA hypomethylation of inflammation-associated genes in adipose tissue of female mice after multigenerational high fat diet feeding
复制标题
多代高脂饮食喂养后雌性小鼠脂肪组织中炎症相关基因 DNA 低甲基化
DOI：
10.1038/ijo.2013.98
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发表时间：
2014-02-01
影响因子：
4.9
通讯作者：
Zheng, L.
中科院分区：
文献类型：
--
作者：
Ding, Y.;Li, J.;Zheng, L.
目的：母亲肥胖可显著增加子代成年后发生肥胖和慢性疾病的易感性。肥胖母亲的后代更喜欢高脂肪饮食（HFD），这是因为他们的神经回路发生了变化，在几代人之间形成了一个“前馈循环”。我们假设，“前馈循环”所造成的多代HFD喂养会加剧的影响，在脂肪tissueofthe children.Methods：三代（F0，F1和F2）的HFD（60%Kcal脂肪）喂养和相应的正常食物（NC）喂养的C57 BL/6小鼠。每周监测体重（BW）和摄食量。在9个月大的雌性后代中测量子宫旁脂肪组织（PAT）重量和内分泌参数。基因表达谱芯片，定量RT-PCR和亚硫酸氢盐测序进行使用pAT。结果：BW和pAT体重增加，在雌性小鼠跨代连续HFD应激下，与F2代中发现的最严重的表型。参与炎症反应的基因在PAT中表现出跨代表达增加，伴随着巨噬细胞浸润增加。Toll样受体1（Tlr 1），Tlr 2和接头的启动子活化的T细胞（Lat）在HF组与NC组相比，与额外的低甲基化的一些特定的CpG位点在F2 generation.Conclusions：一个前馈循环存在于雌性小鼠连续HFD应力后，表现为增加的肥胖和渐进性炎症脂肪组织跨代。DNA低甲基化导致Tlr 1、Tlr 2和Lat的表观遗传学改变的表达，这可能有助于脂肪组织中的炎症。我们的研究为多代HFD喂养应激下脂肪组织炎症增强提供了潜在机制。
Objective:Maternal obesity significantly increases the susceptibility of offspring to develop obesity and chronic diseases in adulthood. The offspring of obese mothers are shown to prefer high fat diet (HFD) due to their altered neural circuitry, creating a ‘feed-forward cycle’across generations. We hypothesized that the ‘feed-forward cycle’caused by multigenerational HFD feeding would have exacerbated effects in adipose tissue of the offspring.Methods:Three generations (F0, F1 and F2) of HFD (60% Kcal fat)-fed and corresponding normal chow (NC)-fed C57BL/6 mice were generated. Body weight (BW) and food intake were monitored weekly. Parametrial adipose tissue (pAT) weight and endocrine parameters were measured in 9-month-old female offspring. Gene expression microarray, quantitative RT-PCR and bisulfite sequencing were performed using pAT.Results:BW and pAT weight increased in female mice across generations under continuous HFD stress, with the most severe phenotype found in the F2 generation. Genes involved in inflammatory response showed increased expression across generations in the pAT, accompanied by increased macrophage infiltration. The promoters of Toll-like receptor 1 (Tlr1), Tlr2 and linker for activation of T cells (Lat) were hypomethylated in the HF groups compared with the NC group, with additional hypomethylation on some specific CpG sites in the F2 generation.Conclusions:A feed-forward cycle exists in female mice after continuous HFD stress as demonstrated by increased adiposity and progressive inflammation in adipose tissue across generations. DNA hypomethylation over generations lead to epigenetically altered expression of Tlr1, Tlr2 and Lat, which may contribute to the inflammation in adipose tissue. Our study provides a potential mechanism for enhanced inflammation in adipose tissue under multigenerational HFD-fed stress.