TXN, a Xanthohumol Derivative, Significantly Attenuates High-Fat Diet Induced Hepatic Steatosis In Vivo by Antagonizing PPARγ

We performed unbiased transcriptional profiling of livers from mice to determine mechanisms by which xanthohumol and tetrahydroxanthohumol supplementation could ameliorate hepatosteatosis induced by a HFD at the transcriptional level. We conducted RNA-seq analysis of total RNA of livers obtained from mice after 16 weeks on the diet. Analysis revealed changes in gene expression that suggested these hop-derived compounds antagonize the nuclear receptor PPARγ. Liver RNA-seq profiling of livers from 26 week old wild type C57BL/6J male mice fed one of four diets for 16 weeks (from age 10 weeks to 26 weeks old): LFD (low fat diet, n = 10), HFD (high fat diet, n = 10), HFD+HXN (xanthohumol 60 mg/kg body weight, n = 10), HFD+TXN (tetrahydroxanthohumol 30 mg/kg body weight, n = 9). HFD group is used as the control/reference group for all analyses.

本研究对小鼠肝脏开展无偏倚转录组分析，旨在从转录水平解析黄腐醇（xanthohumol）与四氢黄腐醇（tetrahydroxanthohumol）补充剂改善高脂饮食（high fat diet, HFD）诱导的肝脂肪变性的分子机制。我们对饲喂对应日粮16周后的小鼠肝脏总RNA进行RNA测序（RNA-seq）分析。分析结果显示，基因表达谱发生显著改变，提示这类啤酒花来源的化合物可拮抗核受体PPARγ。本研究的实验对象为26周龄的野生型C57BL/6J雄性小鼠，自10周龄起分别饲喂四种日粮16周（至26周龄），具体分组为：低脂饮食组（low fat diet, LFD，n=10）、高脂饮食组（high fat diet, HFD, n=10）、高脂饮食+黄腐醇组（简称HFD+HXN，黄腐醇剂量为60 mg/kg体重，n=10）以及高脂饮食+四氢黄腐醇组（简称HFD+TXN，四氢黄腐醇剂量为30 mg/kg体重，n=9）。所有分析均以高脂饮食组（HFD）作为对照/参考组。