Macaca radiata (bonnet monkey): a spontaneous model of nonalcoholic fatty liver disease

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a well-recognized condition that includes a spectrum of clinicopathology conditions ranging from steatotosis to cirrhosis and liver failure. Available animal models are not ideal as they show only a partial resemblance to characteristic human NAFLD. Objective: This study was aimed at identifying a nonhuman primate model of NAFLD resembling features of human NAFLD, which will be useful in understanding the mechanism of the onset of this disease and for developing novel therapeutic modalities. Methods: The histological status of the liver and serum levels of triglycerides (TG), cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of aged bonnet monkeys were compared with that of the aged rhesus and adult bonnet monkeys. Histopathology and immunostaining of liver sections and oil red ‘O’ confirmed NAFLD in aged bonnet monkeys. Results: Aged bonnet monkeys showed a significant (P<0.01) increase in serum TG, AST and ALT compared with aged rhesus and adult bonnet monkeys. Histopathology of the liver of aged bonnet macaques showed diffused microvesicular and macrovesicular fatty changes, perivenular and portal and perisinusoidal fibrosis with fatty degeneration of hepatocytes, and immunostaining of liver sections was suggestive of NAFLD. Conclusion: The spontaneous occurrence of NAFLD in normal animals is rare, but aged bonnet monkeys may serve as a unique animal model for studies related to NAFLD because they mimic pathophysiological features of human NAFLD.