# Lipid metabolism-MAFLD crosstalk: mechanisms and therapy

## TL;DR

This review explores how disrupted lipid metabolism causes MAFLD and suggests new therapeutic strategies to treat it.

## Contribution

The paper systematically summarizes mechanisms of lipid metabolism in MAFLD and highlights recent therapeutic advances.

## Key findings

- Hepatic lipid metabolic dysregulation is central to MAFLD progression.
- Lipidomics and metabolomics reveal specific lipid species linked to MAFLD.
- Therapeutic strategies targeting lipotoxic pathways show promise.

## Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver disorder worldwide, encompassing a spectrum that ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis. However, its precise pathogenic mechanisms remain incompletely understood, and effective, specific pharmacological treatments are still lacking. Disruption of hepatic lipid metabolic homeostasis represents a central event in the onset and progression of MAFLD. With advances in lipidomics and metabolomics, researchers can now more accurately delineate the aberrant accumulation of specific lipid species within hepatocytes and their pivotal roles in triggering insulin resistance, oxidative stress, and inflammatory responses. This review systematically summarizes the core mechanisms by which hepatic lipid metabolic dysregulation drives MAFLD progression and highlights recent advances in therapeutic strategies targeting lipotoxic pathways, metabolic reprogramming, and related molecular targets. These insights aim to provide a theoretical basis and new perspectives for future research and clinical intervention in this field.

This graphical abstract shows MAFLD progression (steatosis to HCC), highlights hepatocyte lipid accumulation and driving mechanisms, outlines interventions, and synthesizes the review’s key pathogenic and therapeutic links.Diagram illustrating the progression of MAFLD, showing core metabolic disorder, cell stress and damage, and inflammation leading to lipid accumulation and stages including MASH, hepatic fibrosis, cirrhosis, and HCC. Disease outcomes and intervention strategies listed are lipotoxicity inhibition, inflammation regulation, metabolic reprogramming, and anti-fibrotic approaches.

This graphical abstract shows MAFLD progression (steatosis to HCC), highlights hepatocyte lipid accumulation and driving mechanisms, outlines interventions, and synthesizes the review’s key pathogenic and therapeutic links.