Deoxycholic Acid and Lipoteichoic Acid cooperatively drive macrophage M2/M1 polarization via TGR5/STAT3 and TLR2/NF-κB to fuel HCC progression in obesity.

ABSTRACT:

Background

Obesity-related hepatocellular carcinoma (HCC) is associated with gut microbiota dysbiosis. However, the specific roles of key microbial metabolites, deoxycholic acid (DCA) and lipoteichoic acid (LTA), in modulating the immune microenvironment and promoting HCC progression are not fully understood.

Aim

This study aimed to elucidate the synergistic effects and mechanisms of DCA and LTA in obesity-related HCC.

Methods

An obesity-related HCC model was established in mice using a high-fat diet combined with diethylnitrosamine. In vitro, macrophage and HCC cell co-culture systems were utilized, along with gene knockdown approaches.

Results

Combined DCA and LTA treatment synergistically exacerbated liver fibrosis and tumorigenesis in the mouse model. This

SUBMITTER: Wu J 

PROVIDER: S-EPMC12723057 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature