The metabolic basis of nonalcoholic steatohepatitis
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and is associated with significant morbidity and mortality worldwide, with a high incidence in Western countries and non‐Western countries that have adopted a Western diet. NAFLD is commonly associated with components...
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Veröffentlicht in: | Endocrinology, diabetes & metabolism diabetes & metabolism, 2020-10, Vol.3 (4), p.e00112-n/a |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and is associated with significant morbidity and mortality worldwide, with a high incidence in Western countries and non‐Western countries that have adopted a Western diet. NAFLD is commonly associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a common mechanistic basis. An inability to metabolically handle free fatty acid overload–metabolic inflexibility–constitutes a core node for NAFLD pathogenesis, with resulting lipotoxicity, mitochondrial dysfunction and cellular stress leading to inflammation, apoptosis and fibrogenesis. These responses can lead to the histological phenotype of nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, which can progress to cirrhosis. This perspective review describes the key cellular and molecular mechanisms of NAFLD and NASH, namely an excessive burden of carbohydrates and fatty acids that contribute to lipotoxicity resulting in hepatocellular injury and fibrogenesis. Understanding the extrahepatic dysmetabolic contributors to NASH is crucial for the development of safe, effective and durable treatment approaches for this increasingly common disease.
Nonalcoholic fatty liver disease (NAFLD) commonly leads to chronic liver disease and is associated with morbidity and mortality, as well as components of metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. The underlying state of metabolic inflexibility with NAFLD may contribute to the development and progression to nonalcoholic steatohepatitis (NASH), which can evolve into cirrhosis and hepatocellular carcinoma. This review describes the key cellular and molecular mechanisms of NAFLD and NASH, namely an excessive burden of carbohydrates and free fatty acids that contributes to lipotoxicity resulting in hepatocellular injury and fibrogenesis. |
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ISSN: | 2398-9238 2398-9238 |
DOI: | 10.1002/edm2.112 |