# Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions.

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/lpi-gpr55-receptor-axis-mafld-insights/
> **Published:** 2026-03-21T12:11:56-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T15:55:22-04:00
> **Clinical Summary:** Explore the LPI GPR55 receptor axis role in MAFLD and MASH, highlighting new research and therapeutic strategies for metabolic liver disease.

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CED Clinical Relevance  #56Monitored Relevance  Early-stage or contextual signal requiring further evidence before action.
Evidence Watch  |  CED Clinic
Mafld[Endocannabinoid System](https://cedclinic.com/endocannabinoid-system-fear-extinction/)Gpr55[Liver Disease](https://cedclinic.com/cannabis-compounds-may-reverse-fatty-liver-disease/)Metabolic Dysfunction

Journal
Liver international: official journal of the International Association for the Study of the Liver

Study Type
[Clinical Study](https://cedclinic.com/cannabis-hyperemesis-syndrome-psychiatric-risk/)

Population
Human participants

Why This Matters

This research identifies a specific cannabinoid-related pathway (LPI/GPR55) that drives progression from fatty liver to more severe inflammatory [liver disease](https://cedclinic.com/cannabis-compounds-may-reverse-fatty-liver-disease/). Understanding this mechanism could lead to targeted interventions for the millions of patients with metabolic liver disease.

Clinical Summary

This [clinical study](https://cedclinic.com/cannabis-hyperemesis-syndrome-psychiatric-risk/) examined the L-α-lysophosphatidylinositol/GPR55 receptor axis, part of the broader [endocannabinoid system](https://cedclinic.com/endocannabinoid-system-fear-extinction/), in human participants with metabolic dysfunction-associated [fatty liver disease](https://cedclinic.com/cannabinoid-receptor-type-1-antagonist-obesity-steatohepatitis/) (MAFLD). The research demonstrates that this pathway promotes harmful liver changes including fat accumulation, inflammation, and scarring across multiple liver cell types. The study also identified that the enzyme MBOAT7 worsens disease progression by modifying this pathway, leading to increased liver fat storage and insulin resistance.

Dr. Caplan’s Take

“While this advances our understanding of how endocannabinoid-related pathways contribute to liver disease, it doesn’t immediately change my clinical approach. The therapeutic implications remain theoretical until we have interventional data.”

Clinical Perspective
Clinicians should recognize that endocannabinoid system dysfunction extends beyond neurological effects to include metabolic liver disease. Patients with MAFLD may benefit from lifestyle interventions that modulate endocannabinoid tone, though specific pharmacological targeting of this pathway awaits further research.

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📰 Source: [https://pubmed.ncbi.nlm.nih.gov/41823054/](https://pubmed.ncbi.nlm.nih.gov/41823054/)

Table of Contents

- [FAQ](#FAQ)[What is the LPI/GPR55 axis, and how does it relate to cannabinoids?](#What_is_the_LPIGPR55_axis_and_how_does_it_relate_to_cannabinoids)
- [How does the LPI/GPR55 pathway affect the liver in fatty liver disease?](#How_does_the_LPIGPR55_pathway_affect_the_liver_in_fatty_liver_disease)
- [What role does the enzyme MBOAT7 play in fatty liver disease?](#What_role_does_the_enzyme_MBOAT7_play_in_fatty_liver_disease)
- [Is there a treatment that targets this pathway for liver disease yet?](#Is_there_a_treatment_that_targets_this_pathway_for_liver_disease_yet)
- [Related](#Related)

## FAQ

### What is the LPI/GPR55 axis, and how does it relate to cannabinoids?

The LPI/GPR55 axis is the L-α-lysophosphatidylinositol/GPR55 receptor axis, which the article describes as part of the broader endocannabinoid system. This research examined the axis in human participants with metabolic dysfunction-associated [fatty liver disease](https://cedclinic.com/cannabinoid-receptor-type-1-antagonist-obesity-steatohepatitis/), known as MAFLD, to understand how this cannabinoid-related pathway contributes to liver disease.

### How does the LPI/GPR55 pathway affect the liver in fatty liver disease?

The article reports that this pathway promotes harmful liver changes, including fat accumulation, inflammation, and scarring, and that these effects occur across multiple types of liver cells. It describes the pathway as driving progression from fatty liver to more severe inflammatory liver disease.

### What role does the enzyme MBOAT7 play in fatty liver disease?

The study identified MBOAT7 as an enzyme that worsens disease progression by modifying the LPI/GPR55 pathway. According to the article, this modification leads to increased fat storage in the liver and to insulin resistance, both of which are part of how MBOAT7 makes metabolic dysfunction-associated fatty liver disease worse.

### Is there a treatment that targets this pathway for liver disease yet?

Not yet. The article says that understanding this mechanism could lead to targeted interventions for the millions of patients with metabolic liver disease, but it presents this as a future possibility. Specific drug treatments aimed at this pathway still await further research, so the findings do not yet translate into a new therapy.

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### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).