近日，国际知名《BioLogy Open》杂志在线发表了中国科学院昆明动物研究所梁斌课题组题为“Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease”的研究论文，研究报道称树鼩是一种非肥胖型脂肪肝动物模型。模型回答了树鼩到底可以作为哪些人类疾病模型。博士研究生张林强为第一作者，梁斌研究员为通讯作者。
非酒精性脂肪肝病目前正在逐渐成为一个严重的公共健康问题，影响着大多数人的健康。随着社会经济的快速发展，生活方式发生改变，大多数人处于高热量食物摄入过多(营养过剩)和长时间久坐等状态，加剧了非酒精性脂肪肝的流行。在欧美等发达国家，大约有20-30%的人患有非酒精性脂肪肝;在中国，有12-24%的人患有同样的疾病。
临床上，非酒精性脂肪肝患者常常伴有肥胖、高血糖、高血脂、胰岛素抵抗甚至还有2型糖尿病等症状，对于这一类非酒精性脂肪肝已经有诸多的动物模型来研究其发病机理。然而，在亚太地区，大约有15-40%，甚至更高的非酒精性脂肪肝患者却并没有表现出肥胖和糖尿病症状，遗憾的是，目前没有合适的动物模型来研究此类非肥胖型非酒精性脂肪肝。
和常用的实验动物大鼠和小鼠相比，树鼩(Tupaia belangeri chinensis)在进化上更加接近灵长类。然而，作为一种新型的实验动物，我们不清楚，树鼩到底可以作为哪些人类疾病动物模型。研究组前期开展了树鼩的体重、血糖、性别和年龄之间的研究，发现它们之间的关系和灵长类、人类很类似，提示树鼩可以作为研究代谢性疾病的动物模型(Relationships between body weight, fasting blood glucose concentration, sex and age in tree shrews (Tupaia belangeri chinensis)）。随后，他们用高脂高胆固醇食物诱导的方法成功建立了树鼩非酒精性脂肪肝动物模型，该模型能够模拟非酒精性脂肪肝的全部发病过程;比小鼠模型相比，其发病时间短，病症显著;并发现脂蛋白脂酶(LPL)在其发病过程中起着关键作用(Cholesterol induces lipoprotein lipase expression in a tree shrew (Tupaia belangeri chinensis) model of non-alcoholic fatty liver disease)。
然而，该模型的一个特点是不肥胖，由此带来的科学问题是，树鼩是否是一种非肥胖型脂肪肝模型?因此，他们使用了4种不同的方法来处理树鼩，每种方法包含有不同高热量食物(如高糖、高脂、高胆固醇、高糖高脂组合)的组合。处理之后，各组树鼩表现出不同程度的肝功能受损，同时伴随有高血脂症，但血糖并未呈现明显变化。进一步通过组织切片检查其肝脏组织发现，所有树鼩都出现肝脏脂肪积累，意味着都成功诱导了脂肪肝。但令人惊奇的是，和对照组树鼩相比，这些脂肪肝树鼩的体重并没有增加，而且在皮下和腹腔等处也没有脂肪组织的出现，说明它们没有出现肥胖，表明树鼩是一种非肥胖型非酒精性脂肪肝动物模型，但其发病机制有待未来继续研究。 研究总结了树鼩可以作为人类非肥胖型脂肪肝模型，用来研究其发病机理和治疗策略
原文链接：
Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease
原文摘要：
Non-alcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of the world population. Generally, NAFLD in patients is usually accompanied by obesity, hyperglycemia, insulin resistance (IR) and type 2 diabetes (T2D), for which numerous animal models have been generated in order to explore the pathogenesis and therapies of NAFLD. On the contrary, quite a number of NAFLD subjects, especially in Asian regions, are non-obese and non-diabetic; however, few animal models are available for the research of non-obese NAFLD. Here, four approaches (here called approach 1 to 4) corresponding to the variable compositions of diets were used to treat tree shrews (Tupaia belangeri chinensis), which have a closer evolutionary relationship to primates than rodents. Analysis of plasma biochemical parameters, hepatic histology, and the expression of hepatic lipid metabolic genes revealed that all four approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia, but had no effect on body weight and adipose tissue generation, or glycemia. Hepatic gene expression in tree shrews treated by approach 4 might suggest a different or non-canonical pathway leading to hepatic steatosis. In conclusion, the tree shrew displays hepatic steatosis and dyslipidemia, but remains non-obese and non-diabetic under high energy diets, which suggests that the tree shrew may be useful as a novel animal model for the research of human non-obese NAFLD.
