Carli Fabrizia, Della Pepa Giuseppe, Sabatini Silvia, Vidal Puig Antonio, Gastaldelli Amalia
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy.
Metabolic Research Laboratories, Medical Research Council Institute of Metabolic Science University of Cambridge, Cambridge CB2 0QQ UK.
JHEP Rep. 2024 Aug 9;6(12):101185. doi: 10.1016/j.jhepr.2024.101185. eCollection 2024 Dec.
Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics. Herein, we review the role of lipid metabolism in MASLD/MASH and discuss the impact of weight loss (diet, bariatric surgery, GLP-1RAs) or other pharmacological treatments (PPAR or THRβ agonists) on hepatic lipid metabolism, lipidomics, and the resolution of MASH.
代谢功能障碍相关脂肪性肝病/脂肪性肝炎（MASLD/MASH）被认为是一种代谢性疾病，其特征是由于脂质溢出和合成导致肝内脂质过度积累，同时这些脂质的氧化和/或输出受损。但这些脂质来自何处？与肝脏脂质积累相关的主要途径是脂肪生成和过多的脂肪酸转运至肝脏（由于脂解增加、脂肪组织胰岛素抵抗以及过多的膳食脂肪酸摄入，尤其是饱和脂肪酸）。脂质组学研究表明，肝脏不仅分泌甘油三酯，还分泌其他脂质，且这些脂质与MASH中更差的组织学特征相关。在此，我们综述脂质代谢在MASLD/MASH中的作用，并讨论体重减轻（饮食、减肥手术、胰高血糖素样肽-1受体激动剂）或其他药物治疗（过氧化物酶体增殖物激活受体或甲状腺激素受体β激动剂）对肝脏脂质代谢、脂质组学以及MASH缓解的影响。
