title: The latest idea in NAFLD/NASH pathogenesis.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by fatty accumulation in the liver without alcohol consumption. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which may progress to end-stage liver disease. The prevalence of NAFLD is rising because of an increasing prevalence of obesity and metabolic syndrome. The progression of these diseases is considered to be related to metabolic syndrome, which is characterized by obesity, glucose impairment, dyslipidemia, hypertension, and adipocytokine impairment. In addition, the pathogenesis of NAFLD/NASH is considered to be multifactorial and complex and is influenced by lifestyle habits, nutritional factors, and genetics. In particular, the PNPLA3 gene has been recently recognized as the most important functional gene polymorphism in the progression of NASH. Disruption in hepatic lipid metabolism is closely related to the development of fatty liver. Accumulation of excess triglycerides (TGs) induces hepatic steatosis. However, TG accumulation itself is not harmful to hepatocytes and may instead act as a protective mechanism against free fatty acid (FFA)-induced lipotoxicity. Excess FFAs also contribute to hepatotoxicity in NAFLD/NASH because oxidation of FFAs in hepatic microsomes generates excessive oxidative stress. Oxidative stress is considered one of the most important pathogenic factors in the development of NASH. Mitochondrial abnormalities, which are frequently observed in NASH-affected livers, are associated with impaired electron transport and result in further oxidative stress formation. The aims of this review are to assess the mechanisms of lipid metabolism and hepatic steatosis, the background of the disease, and the potential molecular mechanisms involved.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan. onom@kochi-u.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
keywords: Adipocytokine impairment; Lipotoxicity; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Oxidative stress; PNPLA3