Early but Not Late Exercise Training in Mice Exacerbates Hepatic Inflammation in Developing Nonalcoholic Fatty Liver Disease

Over 2 billion people worldwide are estimated to have nonalcoholic fatty liver disease(NAFLD),defined by excess hepatic fat.Commonly,progression into nonalcoholic steatohepatitis(NASH)is characterized by the onset of liver inflammation following exacerbated steatosis.1 This suggests that reducing liver inflammation(e.g.through lifestyle interventions involving exercise training)may come secondary to a reduction of steatosis.However,both the metabolic and inflammatory processes involved in NAFLD are under circadian control and could respond differently to exercise at different times of day.2 To investigate the time-of-day–dependent effect of exercise training on NAFLD amelioration in the early disease stages we trained high-fat high-cholesterol(HFHC)-fed APOE*3-Leiden cholesteryl ester transfer protein(CETP)mice during their early or late active period.This mouse model was chosen because of its humanized lipid metabolism and its ability to develop all hallmarks of human NAFLD upon HFHC feeding.

Mouse Models for the Study of Liver Fibrosis Regression In Vivo and Ex Vivo

This review discussed experimental mouse models used in the pre-clinical study of liver fibrosis regression,a pivotal process in preventing the progression of metabolic dysfunction-associated steatohepatitis to irreversible liver cirrhosis.These models provide a valuable resource for understanding the cellular and molecular processes underlying fibrosis regression in different contexts.The primary focus of this review is on the most commonly used models with diet-or hepatotoxin-induced fibrosis,but it also touches upon genetic models and mouse models with biliary atresia or parasiteinduced fibrosis.In addition to emphasizing in vivo models,we briefly summarized current in vitro approaches designed for studying fibrosis regression and provided an outlook on evolving methodologies that aim to refine and reduce the number of experimental animals needed for these studies.Together,these models contribute significantly to unraveling the underlying mechanisms of liver fibrosis regression and offer insights into potential therapeutic interventions.By presenting a comprehensive overview of these models and highlighting their respective advantages and limitations,this review serves as a roadmap for future research.