Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is becoming a severe public health problem that is affecting a large proportion of population in the world. Generally, NAFLD patients are usually accompanied with 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 (approach 1 to 4) divided by the variable compositions of diets were used to treat tree shrews ( Tupaia belangeri chinensis ), which have 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 approaches led to hepatic lipid accumulation, liver injury and hypercholesterolemia; but had no effect on body weight and adipose tissue generation, as well as 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, dyslipidemia, but 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.