Hypothalamic gene expression of appetite regulators in a cancer-cachectic mouse model [Dataset 1]. Mus musculus

Appetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders. Overall design: C26-colon adenocarcinoma cells were subcutaneously inoculated in CDF1 mice. After 20 days, hypothalami were dissected and subjected to gene expression profiling. The total dataset consists of 2 parts; dataset 1, a pilot stuy in which mice were injected with increasing number of tumour cells and pooled samples were arrayed; and dataset 2, the main study in which mice were injected with 1 million tumour cells and samples were individually arrayed.

癌症患者常出现食欲受影响的情况，进而引发厌食症，最终导致食物摄入不足。本研究针对食物摄入增加的癌症恶病质小鼠模型（cancer cachectic mouse model），分析其下丘脑（hypothalamus）基因表达谱（gene expression profile）。在该模型中，接种C26结肠腺癌细胞（C26 colon adenocarcinoma）的小鼠会在体重下降后出现食物摄入增加的情况。我们提出如下假说：在该模型中，下丘脑的食欲调节系统（尽管在厌食症中似乎功能失调）仍可充分适应能量平衡的变化。因此，研究下丘脑食欲调节因子的表达变化，或可揭示癌症诱导性进食障碍的治疗靶点。通过转录组学（transcriptomics）技术，我们可全面分析下丘脑的各类食欲调节系统，从而清晰呈现肿瘤生长过程中下丘脑发生的表达变化。研究结果显示，与对照组相比，荷瘤（TB，tumor-bearing）小鼠下丘脑中促食欲神经肽（orexigenic neuropeptides）NPY与AgRP的表达水平更高，而抑食欲基因（anorexigenic genes）CCK与POMC的表达水平更低。此外，血清素（serotonin）与多巴胺（dopamine）信号通路（signalling pathways）均在荷瘤小鼠中出现显著改变。与对照组小鼠相比，荷瘤小鼠的脑组织血清素水平更低，而多巴胺水平未发生显著变化。此外，脑组织血清素水平与食物摄入量呈负相关。对食物摄入增加的恶病质荷瘤小鼠下丘脑进行转录组分析，结果显示NPY、AgRP以及血清素信号通路均发生了表达变化。脑组织血清素水平与食物摄入量的变化存在相关性。靶向调控这些系统，或可成为预防癌症诱导性进食障碍发生的有效策略。实验整体设计：将C26结肠腺癌细胞皮下接种至CDF1小鼠体内，于接种后20天剥离小鼠下丘脑组织，进行基因表达谱分析。本数据集共包含两部分：数据集1为预实验，实验中向小鼠接种不同梯度数量的肿瘤细胞，并采用混合样本进行基因芯片分析；数据集2为主实验，实验中向小鼠接种100万肿瘤细胞，并采用单个样本分别进行基因芯片分析。