Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting up to 30% of the general adult population. NAFLD encompasses a histological spectrum ranging from pure steatosis to non-alcoholic steatohepatitis (NASH). NASH can progress to cirrhosis and is becoming the most common indication for liver transplantation, as a result of increasing disease prevalence and of the absence of approved treatments. Lipidomic readouts of liver blood and urine samples from experimental models and from NASH patients disclosed an abnormal lipid composition and metabolism. Collectively, these changes impair organelle function and promote cell damage, necro-inflammation and fibrosis, a condition termed lipotoxicity. We will discuss the lipid species and metabolic pathways leading to NASH development and progression to cirrhosis, as well as and those species that can contribute to inflammation resolution and fibrosis regression. We will also focus on emerging lipid-based therapeutic opportunities, including specialized proresolving lipid molecules and macrovesicles contributing to cell-to-cell communication and NASH pathophysiology.

非酒精性脂肪肝病 (NAFLD) 是一种慢性肝病，影响高达 30% 的普通成年人口。NAFLD 涵盖从单纯脂肪变性到非酒精性脂肪性肝炎 (NASH) 的组织学谱。NASH 可进展为肝硬化，并且由于疾病患病率不断增加且缺乏批准的治疗方法，它正在成为肝移植的最常见适应症。对实验模型和 NASH 患者的肝脏血液和尿液样本进行脂质组学读数，发现脂质成分和代谢异常。总的来说，这些变化会损害细胞器功能并促进细胞损伤、坏死性炎症和纤维化，这种情况称为脂毒性。我们将讨论导致 NASH 发展和进展为肝硬化的脂质种类和代谢途径，以及有助于炎症消退和纤维化消退的脂质种类和代谢途径。我们还将重点关注新兴的基于脂质的治疗机会，包括有助于细胞间通讯和 NASH 病理生理学的专门的促溶解脂质分子和大囊泡。