痰湿证肥胖大鼠肾周脂肪基因甲基化特征及温胆汤干预的影响

杨海燕; 喻松仁; 夏循礼; 程绍民; 王萍

doi:10.1016/j.dcmed.2019.09.002

痰湿证肥胖大鼠肾周脂肪基因甲基化特征及温胆汤干预的影响

Methylation Characteristics of Perivisceral Fat Gene in Obese Rats with Phlegm-dampness Syndrome and the Effect of Wen Dan Decoction

摘要

摘要:
目的观察高脂饮食诱导的痰湿证肥胖大鼠肾周脂肪的基因甲基化特征以及温胆汤干预的影响。
方法应用MeDIP-seq法检测基因的甲基化位点情况；采用生物信息学方法分析痰湿证肥胖大鼠的基因甲基化特征及温胆汤干预后对基因甲基化的影响。
结果（1）饮食诱导的痰湿证肥胖大鼠获得3 242个甲基化差异位点，其中甲基化程度下调位点1 243个、上调位点1 999个，涉及1 579个差异基因；GO分析显示“offactory receptor activity”等呈现富集；涉及“Olfactory transduction”等信号通路。（2）温胆汤干预痰湿证肥胖大鼠后，获得甲基化差异位点4 046个，其中下调位点1 067个、上调位点2 979个，涉及2 068个基因；GO分析有“offactory receptor activity”等呈现富集；涉及“Metabolic pathways”等7条信号通路。（3）饮食诱导的痰湿证肥胖大鼠与温胆汤干预后获得甲基化差异基因有582个共同基因；温胆汤干预后的甲基化差异基因涉及GO富集项个数多于痰湿证肥胖大鼠，且同一富集项涉及更多的基因。
结论饮食诱导的痰湿证肥胖大鼠具有基因甲基化改变的特征，温胆汤的干预也能影响基因的甲基化状态。温胆汤干预影响的甲基化基因与饮食诱导的痰湿证肥胖大鼠甲基化改变基因有密切联系，但涵盖范围更为广泛，值得深入探讨。

Abstract:
Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention.
Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegm-dampness syndrome and the effect of Wen Dan Decoction.
Results (1) There were 3 242 methylation differential loci in diet-induced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that " offactory receptor activity” and others were enriched. The possible signal pathways involved were " Olfactory transduction” " Tuberculosis” " Systemic lupus erythematosus” and " Ribosome”. (2) After the intervention of Wen Dan Decoction in obesity with phlegm-dampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as " Metabolic pathways”. (3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes.
Conclusions The phlegm-dampness syndrome of obesity-induced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.

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