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早期单纯性脂肪肝基因组学改变
Liver genomics changes in early stage hepatic steatosis

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DOI:
作者:
慕开达，朱云霞，王士洪，王琛，贾伟平
Mu Kai-da, Zhu Yun-xia, Wang Shi-hong, Wang Chen, Jia Wei-ping
作者单位:
苏州大学医学部（慕开达）；上海交通大学附属第六人民医院内分泌科，上海交通大学糖尿病研究所，上海市糖尿病重点实验室（朱云霞，王士洪，王琛，贾伟平）
Soochow University of Medicine(Mu Kai-da);Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital; Diabetes Institute, Shanghai Jiao Tong University; Shanghai Key Laboratory of Diabetes Mellitus(Zhu Yun-xia, Wang Shi-hong, Wang Chen, Jia Wei-ping)
关键词:
非酒精性脂肪肝；基因芯片；脂代谢；早期脂肪变性
NAFLD; microarray; liqid mitabolism; early stage hepatic steatosis
摘要:
目的 检测轻微脂肪肝患者全基因组表达，探索早期非酒精性脂肪肝（NAFLD）相关基因的改变。方法 肝外科收集肝脏良性疾病的手术标本，肝细胞脂肪变性少于5%作为正常对照组，肝细胞脂肪变性15-25%（轻微脂肪肝）作为脂肪肝组。对照组（n=4）与脂肪肝组（n=4）进行基因芯片检测，差异基因进行生物学分析及实时荧光定量PCR验证。结果 在p<0.05及差异倍数（脂肪肝组/对照组）大于1.4或小于0.7时，得到162条探针，代表128个差异基因。基因富集化分析显示53个基因参与代谢过程。Kegg通路显示脂肪肝组肝脏甘油三酯合成关键酶1酰基甘油3磷酸O酰基转移酶2 （AGPAT2）、甘油激酶（GK）及脂肪酸摄取膜蛋白CD36表达上调，而脂肪酸从头合成通路关键酶乙酰COA酶羧化酶（ACACA）、脂肪酸合成酶（FASN）及脂肪酸延长酶（ELOVL6）表达下调。调控因子——FGF21在脂肪肝组显著上调。脂肪酸β氧化及VLDL分泌通路均无改变。结论 单纯性脂肪肝早期时，脂肪摄取及甘油三酯合成基因上调，但脂肪酸从头合成基因下调，表明脂肪摄取增多及甘油三酯合成增加可能是促进早期NAFLD进展的重要因素。
objective Nonalcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem and is associated with obesity and type 2 diabetes. The pathogenesis of the disorder is not fully clarified. The aim of present study was to evaluate the gene expression in the early stage of NAFLD. Methods The liver tissues were obtained from patients of benign focal hepatic lesions undergoing liver surgery at the Department of Liver Surgery. Affymatrix GeneChip Human Genome U133 Plus 2.0 Array was used to investigate the gene expression in human liver of subjects with early stage liver steatosis (15-25% of hepatocytes with fat) and controls without fatty liver (<5% of hepatocytes with fat). Real-time PCR was used for the confirmation. Results With a threshold of p<0.05 and fold change (fatty liver group/control group)>1.4 or <0.7, we identified 162 probes which represent 128 dif-genes. Among them, 53 genes were involved in metabolic process by Gene ontology analysis. Pathway analysis showed that genes involved in triglyceride synthesis (AGPAT2, GK) and fatty acid transport (CD36) were upregulated, while genes involved in de novo fatty acid synthesis (ACACA, FASN, ELOVL6) were down-regulated in subjects with fatty liver. No changes could be found in genes responsible for β-oxidation and VLDL secretion. Conclusion Increased fatty acid transport and triglyceride synthesis might be the earlier step in the development of NAFLD.

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