Annexin A2 Is Associated with Dietary Cholesterol-Induced Metabolic Dysregulation and the Progression of Hepatic Fibrosis.

Background/

Objectives

Dietary cholesterol intake significantly influences liver health, yet the specific molecular mechanisms by which it accelerates fibrogenesis remain incompletely defined. This study aimed to characterize the dose-dependent effects of dietary cholesterol on hepatic injury and fibrogenesis, identify cholesterol-responsive gene networks through transcriptomic analysis, and investigate Annexin A2 (ANXA2) as a candidate molecular mediator linking dietary cholesterol to hepatic fibrosis progression.

Methods

A CCl4-induced liver fibrosis mouse model was established and supplemented with dietary cholesterol (1-2%). Liver injury and fibrosis were assessed by liver-to-body weight ratios, serum biochemical markers, histological analysis, and fibrogenic gene expression. RNA sequencing combined with multiple hepatic fibrosis database analyses was performed to identify potential molecular mediators.

Results

Dietary cholesterol supplementation aggravated CCl4-induced hepatic fibrosis in mice, with dose-dependent increases in liver-to-body weight ratios and serum AST and ALT levels. Histological analysis showed enhanced collagen deposition and upregulation of fibrogenic genes. By integrating RNA-sequencing with multiple hepatic fibrosis database analysis and correlation analysis, we identified Annexin A2 (ANXA2) as a cholesterol-responsive gene associated with fibrosis.

Conclusions

Dietary cholesterol promotes liver fibrosis progression, and ANXA2 may act as a potential mediator linking cholesterol metabolism to hepatic fibrogenesis.