title: Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease.
abstract: 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Linqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China Key Laboratory of Puer Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, Yunnan 650201, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China School of Life Sciences, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Liao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Pharmaceutical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Ruyue
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Science & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China liangb@mail.kiz.ac.cn.
authors.forename: Bin
authors.identifier: http://orcid.org/0000-0001-9131-5478
authors.initials: B
authors.lastname: Liang
keywords: Animal model; High energy diet; Non-alcoholic fatty liver disease (NAFLD); Non-obese fatty liver; Tree shrew (Tupaia belangeri chinensis)