Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction

• Published in: Revista española de enfermedades digestivas Vol. 98; no. 11; pp. 844 - 874
• Main Authors: Solís Herruzo, J A, García Ruiz, I, Pérez Carreras, M, Muñoz Yagüe, M T
• Format: Journal Article
• Language: English
• Published: Spain Sociedad Española de Patología Digestiva 01-11-2006
• Subjects: Clinical Trials as Topic; Fatty Liver - metabolism; Gastroenterology & Hepatology; Geriatrics & Gerontology; Humans; Infectious Diseases; Insulin Resistance - physiology; Mitochondria, Liver - metabolism; Oncology; Oxidative Stress - physiology; Pathology; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Surgery; Non-alcoholic fatty liver disease; Insulin resistance; Mitochondrial dysfunction
• ISSN: 1130-0108; 1130-0108
• DOI: 10.4321/s1130-01082006001100006

Non-alcoholic fatty liver disease represents a set of liver lesions similar to those induced by alcohol that develop in individuals with no alcohol abuse. When lesions consist of fatty and hydropic degeneration, inflammation, and eventually fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH). The pathogenesis of these lesions is not clearly understood, but they are associated with insulin resistance in most cases. As a result, abdominal fat tissue lipolysis and excessive fatty acid uptake by the liver occur. This, together with a disturbance of triglyceride export as VLDL, results in fatty liver development. Both the inflammatory and hepatocellular degenerative components of NASH are attributed to oxidative stress. Mitochondrial respiratory chain loss of activity plays a critical role in the genesis of latter stress. This may be initiated by an increase in the hepatic TNFalpha, iNOS induction, peroxynitrite formation, tyrosine nitration and inactivation of enzymes making up this chain. Consequences of oxidative stress include: lipid peroxidation in cell membranes, stellate cell activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.