Liu Zhen, Li Qinghe, Liu Ranran, Zhao Guiping, Zhang Yonghong, Zheng Maiqing, Cui Huanxian, Li Peng, Cui Xiaoyan, Liu Jie, Wen Jie
Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China State Key Laboratory of Animal Nutrition, Beijing 100193, P. R. China.
Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R. China College of Animal Science, Jilin University, Changchun 130062, People's Republic of China.
Poult Sci. 2016 Jun 1;95(6):1387-95. doi: 10.3382/ps/pew040. Epub 2016 Apr 14.
The typical characteristic of fatty liver syndrome (FLS) is an increased hepatic triacylglycerol content, and a sudden decline in egg production often occurs. FLS may develop into fatty liver hemorrhagic syndrome (FLHS), characterized by sudden death from hepatic rupture and hemorrhage. DNA methylation is associated with transcriptional silencing, leading to the etiology and pathogenesis of some animal diseases. The roles of DNA methylation in the genesis of FLS, however, are largely unknown. The lipogenic methyl-deficient diet (MDD) caused FLS similar to human nonalcoholic steatohepatitis (NASH). After 16 Jingxing-Huang (JXH) hens were fed MDD for 10 wk, eight exhibited FLS (designated as FLS-susceptible birds); the remainder, without FLS, served as controls (NFLS). Physiological and biochemical variables, gene expression levels, and DNA methylation were determined in the liver. The development of FLS in JXH hens was accompanied by abnormal lipid accumulation. Relative expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and microsomal triglyceride transfer protein (MTTP) were significantly up-regulated in the FLS group in comparison with the NFLS group. The transcript abundance of sterol regulatory element binding protein 1 (SREBP-1c), stearoyl-CoA desaturase (SCD), liver X receptor alpha (LXRα), peroxisome proliferator-activated receptor alpha (PPARα), and peroxisome proliferator-activated receptor gamma (PPARγ) did not differ between the two groups. Interestingly, MTTP and ACC mRNA abundance were negatively correlated with the level of promoter methylation. The extent of DNA methylation of the cytosine-guanine (CpG) sites in the SREBP-1c, FAS, PPARα, and LXRα promoter regions was also analyzed by direct sequencing but none differed between FLS and NFLS birds. Taken together, these results specify link DNA methylation to the pathogenesis of FLS in chickens.
脂肪肝综合征（FLS）的典型特征是肝脏三酰甘油含量增加，且产蛋量常常会突然下降。FLS可能会发展为脂肪肝出血综合征（FLHS），其特征是因肝破裂和出血而突然死亡。DNA甲基化与转录沉默相关，可导致一些动物疾病的病因和发病机制。然而，DNA甲基化在FLS发生过程中的作用在很大程度上尚不清楚。致脂肪生成的甲基缺乏饮食（MDD）会引发与人类非酒精性脂肪性肝炎（NASH）相似的FLS。16只京星黄（JXH）母鸡经10周MDD喂养后，8只表现出FLS（称为FLS易感鸡）；其余未患FLS的作为对照（NFLS）。测定了肝脏中的生理生化变量、基因表达水平和DNA甲基化情况。JXH母鸡FLS的发展伴随着脂质异常蓄积。与NFLS组相比，FLS组中乙酰辅酶A羧化酶（ACC）、脂肪酸合酶（FAS）和微粒体甘油三酯转移蛋白（MTTP）的相对表达显著上调。两组之间固醇调节元件结合蛋白1（SREBP-1c）、硬脂酰辅酶A去饱和酶（SCD）、肝脏X受体α（LXRα）、过氧化物酶体增殖物激活受体α（PPARα）和过氧化物酶体增殖物激活受体γ（PPARγ）的转录本丰度没有差异。有趣的是，MTTP和ACC mRNA丰度与启动子甲基化水平呈负相关。还通过直接测序分析了SREBP-1c、FAS、PPARα和LXRα启动子区域中胞嘧啶-鸟嘌呤（CpG）位点的DNA甲基化程度，但FLS鸡和NFLS鸡之间没有差异。综上所述，这些结果明确了DNA甲基化与鸡FLS发病机制之间的联系。
