Hyperlipidemia is an abnormal elevation of lipid level in blood, which affects more than 100 million people in US. Zebrafish has recently emerged as a model to study pathophysiology associated with hyperlipidemia. As a poikilotherm, the innate response toward a high fat diet regimen in zebrafish is likely to be distinct from humans, and therefore, additional caution is warranted to appropriately interpret results obtained from zebrafish model. However, to date, detailed comparative analyses on similarities and dissimilarities between zebrafish and mammals, in particular, at molecular level, have not been reported yet. Here, we identified changes in hepatic specific transcriptomic profiles of zebrafish fed with a high fat diet regimen and comparatively analyzed transcriptomic changes in zebrafish and mice. While a number of previously identified risk factors for human hyperlipidemia has been upregulated in zebrafish fed with a high fat diet regimen, zebrafish hepatic transcriptome does not share high similarity with mice. Despite these differences, KEGG pathway analyses revealed that similar signaling pathways upregulated in zebrafish and mice as a response to a high fat diet. Our data show that these two species may utilize species-specific set of genes to upregulate common signaling pathways, indicating evolutionary convergence between poikilotherm and homeotherm in regulating lipid metabolism and validating the use of zebrafish as a model for human hyperlipidemia and associated diseases.

高脂血症是血液中脂质水平的异常升高，在美国影响了超过1亿人。斑马鱼最近已成为研究与高脂血症相关的病理生理学的模型。作为poikilotherm，斑马鱼对高脂饮食的先天反应很可能与人类截然不同，因此，需要额外谨慎以适当地解释从斑马鱼模型获得的结果。然而，迄今为止，尚未报道关于斑马鱼与哺乳动物之间，特别是在分子水平上的相似性和不同性的详细比较分析。在这里，我们确定了饲喂高脂饮食方案的斑马鱼肝脏特异性转录组谱的变化，并比较了斑马鱼和小鼠的转录组变化。尽管在高脂饮食喂养的斑马鱼中许多先前确定的人类高脂血症危险因素已被上调，但斑马鱼肝转录组与小鼠的相似性并不高。尽管存在这些差异，但KEGG通路分析表明，类似的信号通路在斑马鱼和小鼠中被上调，作为对高脂饮食的反应。我们的数据表明，这两个物种可能利用特定物种的基因集来上调常见的信号通路，这表明poikilotherm和homeotherm在调节脂质代谢和验证斑马鱼作为人类高脂血症和相关疾病的模型中的进化趋同。斑马鱼肝转录组与小鼠没有高度相似性。尽管存在这些差异，但KEGG通路分析表明，类似的信号通路在斑马鱼和小鼠中被上调，作为对高脂饮食的反应。我们的数据表明，这两个物种可能利用特定物种的基因集来上调常见的信号通路，这表明poikilotherm和homeotherm在调节脂质代谢和验证斑马鱼作为人类高脂血症和相关疾病的模型中的进化趋同。斑马鱼肝转录组与小鼠没有高度相似性。尽管存在这些差异，但KEGG通路分析表明，类似的信号通路在斑马鱼和小鼠中被上调，作为对高脂饮食的反应。我们的数据表明，这两个物种可能利用特定物种的基因集来上调常见的信号通路，这表明poikilotherm和homeotherm在调节脂质代谢和验证斑马鱼作为人类高脂血症和相关疾病的模型中的进化趋同。