Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions - PubMed
7 hours ago
- #MAFLD
- #LPI/GPR55 axis
- #MASH
- MAFLD (Metabolic dysfunction-associated fatty liver disease) is a redefined term for NAFLD, emphasizing metabolic dysfunction in its pathophysiology.
- The LPI/GPR55 axis, part of the endocannabinoidome, plays a key role in liver disease progression, leading to MASH (metabolic dysfunction-associated steatohepatitis).
- This axis contributes to hepatic lipid accumulation, inflammation, fibrosis, and de novo lipogenesis, promoting liver steatosis.
- MBOAT7 enzyme modulates the LPI/GPR55 axis, worsening hepatic steatosis and insulin resistance.
- Recent FDA-approved treatments for MASH include resmetirom (March 2024) and semaglutide (August 2025), with other agents like tirzepatide and retatrutide in late-stage clinical trials.
- Targeting the LPI/GPR55 axis is a promising therapeutic strategy, though challenges remain due to GPR55's context-specific roles across tissues.
- Future strategies should focus on hepatic-specific GPR55 modulation using selective ligands and advanced delivery systems to minimize off-target effects.