Psammomys obesus (sand rat), a new animal model of non-alcoholic fatty liver disease

Abstract

Background/aims Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that includes a spectrum of clinicopathologic conditions ranging from steatotosis to cirrhosis and liver failure. NAFLD is usually associated with features of the metabolic syndrome. No established therapies can be offered to patients with NAFLD. An appropriate animal model of NAFLD would be of help in understanding the mechanisms of the disease and in testing novel therapeutic modalities. Available animal models, such as ob/ob and db/db mice, are unsatisfactory since they show only partial resemblance to human NAFLD. Psammomys obesus (sand rat) is a well-established model of type-2 diabetes and obesity, which shares most metabolic parameters of the human metabolic syndrome. In the present study, we hypothesized that P. obesus will also show features of non-alcoholic fatty liver disease. Methods Experimental and control animals were fed normal rat chow or either chow to which fiber (30% wheat straw) was added for 6–18 weeks. Body weight and capillary glucose were measured regularly. At sacrifice blood samples, liver and epididymal fat were obtained. Histology of the liver was blindly determined by a pathologist. Results The experimental group showed increased body weight, liver and abdominal fat pad mass, raised plasma glucose, insulin and lipids. Also, alanine-aminotransferase (189 ± 76 IU versus 86 ± 26 IU; p < 0.0001) was significantly higher in the experimental than the control group. Microscopic examination of liver tissue demonstrated marked macrovesicular fat infiltration in the experimental group while it was histologicaly normal in the control animals (liver fat score 1.7 ± 1.0 and 0.2 ± 0.4; p < 0.0001, respectively). Conclusions Fed a calorie-rich diet P. obesus develops a syndrome, which shares metabolic, laboratory and histopathologic characteristics compatible with human NAFLD.