Liver transcriptome comparison of divergently selected Lean and Fat mouse lines in cholesterol homeostasis, bile acids, glucose and lipoprotein metabolism

This study aimed to identify molecular basis of obesity-resistant mechanisms in the Lean line with the emphasis on lipid homeostasis. Expression profiling using custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol synthesis genes compared to the Fat line. A significant difference between the strains was also found in the bile acid metabolism. We identified novel candidate molecular targets by which we can at least in part explain resistance to obesity development in the Lean line. Direct comparison of 10 Lean and 10 Fat mouse samples. For 7 out of 10 comparisons dye-swap technical replication were performed.本研究旨在明确肥胖抵抗品系（Lean line）的肥胖抵抗机制的分子基础，重点关注脂质稳态（lipid homeostasis）。采用定制化Steroltalk v2基因芯片开展表达谱分析，结果显示，相较于肥胖易感品系（Fat line）小鼠，肥胖抵抗品系小鼠肝脏内的胆固醇合成相关基因表达水平显著更高。两个品系在胆汁酸代谢方面同样存在显著差异。本研究鉴定出了全新的候选分子靶点，可至少部分阐释肥胖抵抗品系小鼠的肥胖抵抗发生机制。本研究直接比对了10例肥胖抵抗品系小鼠样本与10例肥胖易感品系小鼠样本，在10组比对实验中，有7组完成了染料互换技术重复（dye-swap technical replication）。