Lipid metabolism in MASLD and MASH: From mechanism to the clinic

IF 9.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2024-08-09 DOI:10.1016/j.jhepr.2024.101185

Fabrizia Carli , Giuseppe Della Pepa , Silvia Sabatini , Antonio Vidal Puig , Amalia Gastaldelli

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Abstract

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 de novo 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.

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MASLD 和 MASH 的脂质代谢：从机制到临床

代谢功能障碍相关性脂肪性肝病/脂肪性肝炎（MASLD/MASH）被认为是一种代谢性疾病，其特点是由于脂质溢出和合成导致肝内脂质过量积聚，同时这些脂质的氧化和/或输出功能受损。但这些脂质从何而来？与肝脏脂质积聚有关的主要途径是新生脂肪生成和向肝脏运输过量脂肪酸（由于脂肪分解增加、脂肪组织胰岛素抵抗以及饮食中摄入过量脂肪酸，尤其是饱和脂肪酸）。肝脏分泌的不仅是甘油三酯，还有其他脂类，正如脂质组学所显示的那样，这些脂类与 MASH 组织学特征的恶化有关。在此，我们回顾了脂质代谢在 MASLD/MASH 中的作用，并讨论了减肥（饮食、减肥手术、GLP-1RAs）或其他药物治疗（PPAR 或 THRβ 激动剂）对肝脏脂质代谢、脂质组学和 MASH 的缓解的影响。

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来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.