Development of steatohepatitis in Ob/Ob mice is dependent on Toll-like receptor 4
Journal Title: Annals of Hepatology - Year 2015, Vol 14, Issue 5
Abstract
Background and aim. The etiology of non-alcoholic fatty liver disease (NAFLD) progression, and why some patients develop non-alcoholic steatohepatitis (NASH) vs. uncomplicated NAFLD, is not well understood. Obesity and NAFLD are thought to be associated with high circulating levels of leptin; however, the role of leptin in NASH has been controversial. Secondly, as ob/ob mice are known to have elevated circulating levels of TLR4-stimulating endotoxin secondary to increased intestinal permeability. Material and methods. We evaluated the long-term effects of steatosis on the livers of aleptinemic (OB) mice and the role of TLR4 in the development of hepatic sequelae in these animals. Results. At 20 weeks of age OB animals displayed grossly steatotic livers, but also features of early stage NASH including hepatocellular ballooning and numerous necroinflammatory foci with associated changes in serum aspartate aminotransferase (AST) and alanine transaminase (ALT). TLR4 KO did not affect the development of obesity or steatosis in ob/ob mice, but protected these animals from hepatitis and liver injury. Conclusions. In conclusion, the data presented here indicate that steatohepatitis develops in the absence of leptin, and that TLR4 is integral to the development NASH secondary to hyperphagia.
Authors and Affiliations
Alton G. Sutter, Arun P. Palanisamy, Julie H. Lench, Alex P. Jessmore, Kenneth D. Chavin
Keywords
Related Articles
- EP ID EP78500
- DOI -
- Views 123
- Downloads 0
Predicting early discharge from hospital after liver transplantation (ERDALT) at a single center: a new model
Background & rationale. Limited information related to Liver Transplantation (LT) costs in South America exists. Additionally, costs analysis from developed countries may not provide comparable models for tho...
title
abstrakt<br/><br/>
HAV and HBV seroprevalence in 1,000 patients with chronic HCV infection in a Tertiary Care Center in São Paulo, Brazil
Background. Patients with chronic HCV infection and superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when compared with those without HCV infection. Therefore, HAV...
Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside
Oxidative stress is importantly involved in the pathophysiology of various liver diseases. The redox state participates on the courseof the inflammatory, metabolic and proliferative liver diseases. The main sources of t...
Early treatment with N-acetylcysteine in <br /> children with acute liver failure secondary to hepatitis A<br />
Introduction. Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed. Objective. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure a...