Altered HDL Phospholipid and Fatty Acid Profile in MASLD: A Possible Explanation for the Increased CVD Risk

Area of Science:

• Cardiovascular Medicine
• Hepatology
• Lipidology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing concern, frequently associated with an elevated risk of cardiovascular disease (CVD).
• High-density lipoprotein (HDL) particles, known for their atheroprotective properties and hepatic synthesis, are implicated as a potential mediator in the MASLD-CVD link.

Purpose of the Study:

• To investigate the lipid composition of HDL lipoproteins in patients with MASLD compared to healthy controls and patients with coronary artery disease (CAD).
• To explore how alterations in HDL lipid profiles in MASLD may contribute to the increased cardiovascular risk.

Main Methods:

• Serum samples were analyzed from 51 MASLD patients, 40 CAD patients, and 50 healthy controls.
• HDL lipid profiles were characterized using proton nuclear magnetic resonance (¹H NMR) spectroscopy.

Main Results:

• MASLD patients displayed increased lysophosphatidylcholine and sphingolipid content (notably ceramides), with reduced phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol compared to controls.
• A decrease in polyunsaturated fatty acids (linoleic, docosahexaenoic, eicosapentaenoic, arachidonic) and an increase in saturated fatty acids were observed in MASLD patients' HDL, more pronounced than in CAD patients.
• MASLD patients showed higher sphingolipids, ceramides, and glycerolipids, and lower phosphatidylinositol compared to CAD patients.

Conclusions:

• The observed changes in HDL lipid composition in MASLD patients, including altered fatty acid profiles and increased sphingolipids, may compromise HDL's atheroprotective functions.
• These HDL modifications represent a potential mechanism linking MASLD to an increased risk of cardiovascular disease.