Genetically modified mouse models for the study of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.

Transcriptomic and pathological profiling of a new congenic mouse model with Lepr mutation:Evaluating susceptibility to the development of obesity and NAFLD

Non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)are two disease conditions for which obesity is a risk factor.^(1)Due to the close relationship between the three pathologies,researchers frequently use the same mouse models to identify the underlying processes of obesity,NAFLD,and T2DM.For instance,leptin(Lep)-null(ob/ob)and leptin receptor(Lepr)-deficient(db/db)mice spontaneously develop NAFLD and show different phenotypes of extreme obesity and diabetes,respectively.