Lipid metabolism in MASLD and MASH: From mechanism to the clinicKeypoints
Fabrizia Carli,
Giuseppe Della Pepa,
Silvia Sabatini,
Antonio Vidal Puig,
Amalia Gastaldelli
Affiliations
Fabrizia Carli
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy
Giuseppe Della Pepa
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy
Silvia Sabatini
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy
Antonio Vidal Puig
Metabolic Research Laboratories, Medical Research Council Institute of Metabolic Science University of Cambridge, Cambridge CB2 0QQ UK; Centro de Investigacion Principe Felipe Valencia 46012 Spain; Cambridge University Nanjing Centre of Technology and Innovation, Nanjing, China
Amalia Gastaldelli
Cardiometabolic Risk Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy; Corresponding author. Address: Institute of Clinical Physiology, CNR, Via Giuseppe Moruzzi 1, 56124 Pisa Italy.
Summary: 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.
