Effect of physical training in non-alcoholic steatohepatitis (NASH) in obese mice

• Grant number: 13/07030-2
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2013
• Effective date (End): July 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Claudia Pinto Marques Souza de Oliveira
• Grantee: Bruna Roberta Muntanelli
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common form of liver disease, primarily related to increasing obesity in the world. Due to rising rates of obesity, NAFLD is becoming increasingly common in all populations, especially in the Western world and has been defined by experts as a disease of the modern world. NAFLD encompasses a spectrum of liver abnormalities ranging from simple fatty deposits inside the hepatocyte, without inflammation or fibrosis (simple steatosis), to nonalcoholic steatohepatitis cases (NASH), cirrhosis, and hepatocellular carcinoma in patients with no history of alcoholism. Various approaches are used in the treatment of NAFLD and these are based on the treatment of conditions associated as obesity, diabetes and hypertriglyceridemia, and discontinuation of hepatotoxic drugs. The recommendation of the loss of excess weight and exercise should always be recommended, regardless of histological grade of liver biopsy of the patient. One of the factors recommended in the treatment of NASH is aerobic exercise due to the increased rate of lipolysis and weight reduction. Animal studies have helped in the understanding of the pathophysiological mechanisms and treatment of NAFLD. Currently there are several animal models for studying NAFLD and NASH. Among the major models highlight the obese mouse model deficient in leptin (LEP ob / ob) that carries metabolic syndrome. feature with obesity metabolic disorders similar to those of diabetics. However, this animal does not develop NASH spontaneously, requiring a second stimulus that becomes steatosis steatohepatitis needing a stimulus as degundo hypercaloric diets deficient or choline to induce NAFLD. Implemented in our environment, in previous work, the experimental model of non-alcoholic steatohepatitis induced by both DCM diet as fat diet (HFD), both in obese mice (Oliveira et al, 2008). Was achieved with these models, develop nonalcoholic steatohepatitis very similar to the human form, with hepatocellular ballooning, microvesicular steatosis and macro in zone III (central vein), and infiltration of polymorphonuclear satellitosis. Considering the beneficial effects of physical training to promote metabolic adaptations that may contribute directly to the treatment of NAFLD, and the opportunity to study an animal model that develops robustly hepatic pathological phenotype by using diet, this work will be order to investigate the role of aerobic exercise for treatment of NAFLD and the cellular mechanisms involved in this response. (AU)