Expression data from livers of F2 mice (B57BL/6 X DBA/2) deficient in leptin receptor (db/db)

In several models of obesity-induced diabetes, increased lipid accumulation in the liver has been associated with decreased diabetes susceptibility. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and C57BLKS mice but, only on the C57BLKS background do the mice develop beta-cell loss leading to severe diabetes while C57BL/6 mice are relatively resistant. Liver triglyceride levels in the resistant C57BL/6 mice are 3 to 4 fold higher than in C57BLKS. To better understand the mechanisms contributing to metabolic dysfunction in obesity-induced diabetes, we used microarrays to comprehensively profile gene expression livers of F2 mice (B57BL/6 X DBA/2) deficient in leptin receptor (db/db) DBA/2J females were mated to C57BL/6 males carrying leptin receptor deficiency (db/+) and, F1 (db/+) offspring were interbred to produce F2 mice. Offspring deficient in leptin receptor (db/db) were fed on a chow diet until 5 weeks or 12 weeks of age and then euthanized for collection of liver tissue for RNA profiling along with other diabetes-related phenotypes.在多种肥胖诱导型糖尿病模型中，肝脏脂质蓄积增加与糖尿病易感性降低存在关联。例如，瘦素受体（leptin receptor）缺陷（db/db）可使C57BL/6与C57BLKS两种小鼠均出现多食症与肥胖，但仅在C57BLKS遗传背景下，小鼠才会发生胰岛β细胞丢失进而引发重度糖尿病，而C57BL/6小鼠则相对抵抗该病症。具有病症抵抗性的C57BL/6小鼠，其肝脏甘油三酯水平较C57BLKS小鼠高3至4倍。为深入阐明肥胖诱导型糖尿病中代谢功能异常的潜在机制，本研究利用基因芯片（microarrays）技术，对瘦素受体缺陷（db/db）的F2代小鼠（B57BL/6 × DBA/2）的肝脏基因表达进行全面谱学分析。实验繁育策略如下：将DBA/2J雌性小鼠与携带瘦素受体缺陷（db/+）的C57BL/6雄性小鼠交配，所得F1代（db/+）个体再进行互交，从而获得F2代小鼠。将瘦素受体缺陷（db/db）的子代小鼠饲喂普通维持饲料，分别于5周龄和12周龄时实施安乐死，收集肝脏组织用于RNA表达谱分析，并同步检测其他糖尿病相关表型。