# ATP6V1B2 alleviates hepatic steatosis by promoting lysosomal acidification in hepatocytes

## TL;DR

This study shows that ATP6V1B2 helps reduce liver fat by maintaining lysosomal acidity, offering a new target for treating liver disease.

## Contribution

The novel finding is that ATP6V1B2 regulates lipid metabolism via lysosomal acidification and FASN degradation.

## Key findings

- Reduced ATP6V1B2 expression in MASLD patients correlates with increased liver lipid accumulation.
- ATP6V1B2 maintains lysosomal acidity, which is essential for degrading fatty acid synthase (FASN).

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic disorder characterized by the abnormal accumulation of fat in the liver. ATP6V1B2, an essential subunit of the vacuolar ATPase (V-ATPase) complex, plays a pivotal role in its function and assembly. Despite its importance, the regulatory role of ATP6V1B2 and its molecular mechanism in MASLD progression remain poorly understood. In this study, we observed a significant reduction in ATP6V1B2 expression in the serum of MASLD patients. Experimental results demonstrated that inhibiting ATP6V1B2 expression in liver cells led to increased lipid accumulation, aggravated oxidative stress, upregulation of fatty acid synthase (FASN), and impaired autophagic activity. Further investigation revealed that ATP6V1B2 promotes the lysosomal degradation of FASN by maintaining the acidic environment of lysosomes, thereby playing a crucial role in lipid metabolism regulation. These findings uncover the critical mechanism by which ATP6V1B2 contributes to MASLD development and suggest that restoring its function could offer novel therapeutic strategies for treating this condition.