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.