Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States.
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States.
Front Endocrinol (Lausanne). 2021 May 10;12:665987. doi: 10.3389/fendo.2021.665987. eCollection 2021.
Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide in the past few decades as a consequence of the global obesity epidemic and is associated with significant morbidity and mortality. NAFLD is closely associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a plausible metabolic mechanistic basis. Metabolic inflexibility is considered a nidus for NAFLD pathogenesis, causing lipotoxicity, mitochondrial dysfunction and cellular stress leading to inflammation, apoptosis and fibrogenesis, thus mediating disease progression into nonalcoholic steatohepatitis (NASH) and ultimately cirrhosis. In this review, we describe they key metabolic drivers that contribute to development of NAFLD and NASH, and we explain how NASH is a metabolic disease. Understanding the metabolic basis of NASH is crucial for the prevention and treatment of this disease.
非酒精性脂肪性肝病（NAFLD）在过去几十年中已成为全球慢性肝病的主要病因，这是由于全球肥胖症的流行，且与显著的发病率和死亡率相关。NAFLD 与代谢综合征的成分、2 型糖尿病和心血管疾病密切相关，这提示了一种合理的代谢机制基础。代谢灵活性差被认为是 NAFLD 发病机制的核心，导致脂毒性、线粒体功能障碍和细胞应激，从而导致炎症、细胞凋亡和纤维化，进而介导疾病进展为非酒精性脂肪性肝炎（NASH），最终发展为肝硬化。在这篇综述中，我们描述了导致 NAFLD 和 NASH 发生的关键代谢驱动因素，并解释了为什么 NASH 是一种代谢疾病。了解 NASH 的代谢基础对于预防和治疗这种疾病至关重要。
