Male mus musculus transcriptomes from whole liver tissue

The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system's complement cascade, and were supported by the proteome and histological staining. Overall design: For RNA-sequencing, we used 4 animals for each experimental group, and we had 8 experimental groups, all of which were male mice. The groups were: [1] wildtype mice on a control-ketogenic diet (CD) fasted for 4 hours, [2] wildtype mice on a ketogenic diet (KD) fasted for 4 hours, [3] wildtype mice on a control-ketogenic diet (CD) fasted for 24 hours, [4] wildtype mice on a ketogenic diet (KD) fasted for 24 hours, [5] Fatp2-/- mice on a control-ketogenic diet (CD) fasted for 4 hours, [6] Fatp2-/- mice on a ketogenic diet (KD) fasted for 4 hours, [7] Fatp2-/- mice on a control-ketogenic diet (CD) fasted for 24 hours, and [8] Fatp2-/- mice on a ketogenic diet (KD) fasted for 24 hours,

生酮饮食（ketogenic diet）在受体重增加困扰的患者中已被证实可有效促进减重。其作用机制在于引发代谢层面的细胞能量来源转换，以肝脏衍生的酮体作为主要供能物质，而非葡萄糖。脂肪酸转运蛋白2（Fatty acid transport protein 2, FATP2）在肝脏、小肠与肾脏中呈高表达状态，其功能涵盖外源性长链脂肪酸（long chain fatty acids, LCFA）的转运，以及极长链脂肪酸（very long chain fatty acids, VLCFA）向辅酶A硫酯的活化过程。本团队完成了一项针对FATP2敲除（Fatp2-/-）小鼠的多组学研究，实验小鼠分别饲喂生酮饮食（ketogenic diet, KD）或配对对照饮食（control diet, CD），并设置24小时禁食亚组（KD禁食组与CD禁食组），旨在探究FATP2敲除在高应激条件下的生物学影响。野生型（wt/wt）与Fatp2-/-小鼠分别饲喂对应饮食，持续饲养4周。随后将半数小鼠处死，剩余个体在处死前禁食24小时。后续我们对全肝组织开展双端RNA测序（RNA-sequencing），以分析差异基因表达情况。差异表达基因富集于氨基酸及其衍生物代谢、脂肪酸代谢、蛋白质定位以及免疫系统补体级联反应等基因本体（ontology）条目，相关结果得到了蛋白质组学与组织化学染色数据的验证。实验整体设计如下：本次RNA测序的每个实验组均使用4只雄性小鼠，共设置8个实验组，具体分组为：[1] 饲喂对照饮食（CD）且禁食4小时的野生型小鼠；[2] 饲喂生酮饮食（KD）且禁食4小时的野生型小鼠；[3] 饲喂对照饮食（CD）且禁食24小时的野生型小鼠；[4] 饲喂生酮饮食（KD）且禁食24小时的野生型小鼠；[5] 饲喂对照饮食（CD）且禁食4小时的Fatp2-/-小鼠；[6] 饲喂生酮饮食（KD）且禁食4小时的Fatp2-/-小鼠；[7] 饲喂对照饮食（CD）且禁食24小时的Fatp2-/-小鼠；[8] 饲喂生酮饮食（KD）且禁食24小时的Fatp2-/-小鼠。