The role of mTOR in the progression of non-alcoholic fatty liver disease

Identifier:  TFG:1632

Handle: https://hdl.handle.net/20.500.11797/TFG1632

Authors:  Martínez Esteve, Elia

Abstract:
In recent years there has been an increase in the incidence of obesity and the associated comorbidities, such as NAFLD. This pathology covers a spectrum of liver damage, which includes steatosis and steatohepatitis, even leading to liver cirrhosis or hepatocarcinoma. NAFLD is also a metabolic pathology, so that both energy metabolism and mitochondrial dysfunction play a crucial role in its development. For this reason, our objective was to evaluate the role of mTOR in the progression of NAFLD and its relationship with energy metabolism and autophagy. During the study, the clinical, biochemical and histological parameters of a study group formed by 270 patients with class III obesity were evaluated. Patients were classified according to the progression of NAFLD they presented to make a comparison between the expression profiles of AMPK, mTORC1 and some components of the autophagy machinery using Western Blot. The status of liver mitochondria was also compared by transmission electron microscopy (TEM). Significant differences were observed in liver status and biochemical parameters between NAFL patients and NASH patients. In addition, NASH patients showed lower activation of AMPK and increased activation of mTORC1. Therefore, the autophagy process was significantly reduced in NASH patients compared to NAFL. In conclusion, it has been established that mitochondrial dysfunction and the reduction of the autophagy process associated with hepatic steatosis play a fundamental role in the progression of NAFLD to NASH.