Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis.
Rich diet and lack of exercise are causing a surge in the prevalence of obesity and hepatic steatosis, which causes "primary" steatohepatitis in some patients. Ultrastructural mitochondrial lesions, decreased activity of respiratory chain complexes, and impaired ability to synthesize ATP are observed in these patients. Reactive oxygen species (ROS) may increase tumor necrosis factor-alpha (TNF-alpha) production and also oxidize fat deposits. TNF-alpha and lipid peroxidation products impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial ROS formation. Steatohepatitis can also be due to alcohol, drugs, or other causes that either directly increase ROS formation or first impair respiration, which secondarily increases ROS formation. Higher ROS formation in secondary steatohepatitis could cause more lipid peroxidation, cytokine induction, and fibrogenesis than in primary steatohepatitis.
Pessayre
Dominique
D
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 481, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92118 Clichy, France. pessayre@bichat.inserm.fr
Mansouri
Abdellah
A
Fromenty
Bernard
B
D005223:Fats / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism*; D006505:Hepatitis / Q000150:complications / Q000378:metabolism*; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D005223:Fats; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase