# Ferulic acid inhibits lipogenesis and ameliorates MASLD via targeting PGC-1β

## TL;DR

Ferulic acid, a plant compound, reduces liver fat by targeting PGC-1β, offering a new treatment for metabolic liver disease.

## Contribution

Identifies PGC-1β as a novel target for MASLD treatment via ferulic acid's inhibition of lipogenesis.

## Key findings

- Ferulic acid improves MASLD in mice and cell models by inhibiting PGC-1β.
- FA binds to PGC-1β and reduces its expression through the ubiquitin-proteasome pathway.
- PGC-1β overexpression reverses the beneficial effects of FA on MASLD.

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and increased triglyceride content. Thus, intervention in fatty acid metabolism is very desirable for NAFLD treatment. Ferulic acid (FA) is a plant-derived bioactive molecule that regulates lipid metabolism.

High-fat diet (HFD)-fed mice and free fatty acid (FFA) -treated cells were used to evaluate the improvement of FA. The target proteins of FA were screened by solid phase extraction combined with mass spectrometry.

It was found that FA effectively improved MASLD in vivo and in vitro. Interestingly, PPAR gamma-coactivator-1beta (Ppargc1β, also known as PGC-1β) was the target of FA intervention in MASLD. FA directly bound to PGC-1β and inhibited its expression through the ubiquitin-proteasome pathway. Furthermore, Overexpression of PGC-1β abolished the ameliorative effect of FA on MASLD. In addition, FA inhibited lipogenesis through the PGC-1β/SREBP1 axis, thereby improving MASLD.

This work uncovered a novel plant-derived therapeutic strategy targeting a previously unrecognized PGC-1β/SREBP1 mechanism in MASLD.

Diagram illustrating the molecular mechanism of FA ameliorates MASLD. FA directly binds to and inhibits the expression of PGC-1β protein through the ubiquitin–proteasome pathway. FA inhibits lipogenesis through the PGC-1β/SREBP1 axis, thereby improving MASLD. Hence, PGC-1β serves as an underlying target for FA to improve MASLD.Diagram of cellular lipogenesis process. Fatty acids (FA) enter the cytosol, interacting with PGC-1β molecules. Ubiquitination (Ub) modifies these molecules, influencing SREBP1 in the nucleus. This action leads to transcription and translation at the transcription start site (TSS), resulting in lipid accumulation.

Diagram illustrating the molecular mechanism of FA ameliorates MASLD. FA directly binds to and inhibits the expression of PGC-1β protein through the ubiquitin–proteasome pathway. FA inhibits lipogenesis through the PGC-1β/SREBP1 axis, thereby improving MASLD. Hence, PGC-1β serves as an underlying target for FA to improve MASLD.