Animal models of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, accompanying the rise in obesity and its related metabolic disorders. Though research in the field is vibrant, enormous gaps in knowledge still remain about its physiology, how to identify patients who are most susceptible for adverse outcomes, and the best therapeutic approach. It is difficult to study NAFLD in humans, since the disease evolves slowly and encompasses diverse liver phenotypes that are challenging to differentiate noninvasively. Steatosis is the most clinically benign NAFLD phenotype, while nonalcoholic steatohepatitis (NASH) has a much more variable prognosis that seems to depend upon the severity of hepatocyte injury and propensity for progressive fibrosis. NASH patients in whom fibrosis progresses to cirrhosis ultimately develop the worst liver-related outcomes because cirrhosis increases the risk for primary liver cancer, liver-related morbidity, and death from liver disease. Animal models that mimic the spectrum of human NAFLD pathology are crucial to overcome the challenges inherent in human NAFLD research so that knowledge about this disease can advance. There are many animal models for NAFLD, none of them perfect. Some are more suitable for studying the metabolic derangements, others for studying inflammation and fibrogenesis. The most used animals are rodents, particularly mice. NAFLD can be induced through specific diets or through genetic manipulation. This chapter will review the different animal models available, with a critical appraisal of their advantages and limitations.

Duke Scholars

Author Anna Mae Diehl Medicine, Gastroenterology