ABCA1 deficiency‐induced cholesterol accumulation aggravates colonic epithelial injury in knockout hamsters
4 affiliations
- 1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China
- 2Institute of Laboratory Animal Science, CAMS & PUMC Beijing China
- 3Guangdong Province Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering Wuyi University Jiangmen China
- 4Peking University Institute of Cardiovascular Sciences Beijing China
Abstract
Background: ATP‐binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux, yet its role in inflammatory bowel disease (IBD) remains incompletely understood. This study investigated the consequences of intestinal epithelial cholesterol accumulation—primarily driven by ABCA1 deficiency—on colonic inflammation and the underlying molecular mechanisms.
Methods: ABCA1 knockout (KO) and wild‐type (WT) Syrian golden hamsters were fed a high‐cholesterol high‐fat diet for 12 weeks. Colon specimens were analyzed for pathological changes, inflammatory markers, cholesterol accumulation, and gene expression profiles. Furthermore, in vitro experiments were performed using the human colon epithelial cell line Caco‐2.
Results: ABCA1 deficiency, in the context of a high‐cholesterol high‐fat diet, triggered significant colonic inflammation in KO hamsters, characterized by epithelial damage, inflammatory cell infiltration, and elevated pro‐inflammatory cytokine levels. These pathological changes were associated with impaired mucosal barrier integrity, a four‐fold increase in epithelial cholesterol accumulation, and reduced E‐cadherin, ZO‐1 and occludin expression. Furthermore, ABCA1 deficiency promoted oxidative stress and induced marked remodeling of the gut microbiota.
Conclusions: Our findings establish a pathogenic role for ABCA1 deficiency in driving colonic epithelial injury and inflammation, suggesting that ABCA1 may play an important role in the pathogenesis of IBD.
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BibTeX
@article{liu2026abca1,
title = {{ABCA1 deficiency‐induced cholesterol accumulation aggravates colonic epithelial injury in knockout hamsters}},
author = {Chang Liu and Jingjie Zheng and Sijing Shi and Jianwen Chen and Geroge Liu and Wei Huang and Xunde Xian and Yuhui Wang and Jianglin Fan and Ping Zhu and Xiawen Yang},
journal = {Animal models and experimental medicine},
year = {2026},
month = oct,
doi = {10.1002/ame2.70301},
url = {https://europepmc.org/article/PMC/PMC13673243},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - ABCA1 deficiency‐induced cholesterol accumulation aggravates colonic epithelial injury in knockout hamsters
AU - Chang Liu
AU - Jingjie Zheng
AU - Sijing Shi
AU - Jianwen Chen
AU - Geroge Liu
AU - Wei Huang
AU - Xunde Xian
AU - Yuhui Wang
AU - Jianglin Fan
AU - Ping Zhu
AU - Xiawen Yang
PY - 2026
DA - 2026/10/16
JO - Animal models and experimental medicine
DO - 10.1002/ame2.70301
UR - https://europepmc.org/article/PMC/PMC13673243
AB - Background: ATP‐binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux, yet its role in inflammatory bowel disease (IBD) remains incompletely understood. This study investigated the consequences of intestinal epithelial cholesterol accumulation—primarily driven by ABCA1 deficiency—on colonic inflammation and the underlying molecular mechanisms. Methods: ABCA1 knockout (KO) and wild‐type (WT) Syrian golden hamsters were fed a high‐cholesterol high‐fat diet for 12 weeks. Colon specimens were analyzed for pathological changes, inflammatory markers, cholesterol accumulation, and gene expression profiles. Furthermore, in vitro experiments were performed using the human colon epithelial cell line Caco‐2. Results: ABCA1 deficiency, in the context of a high‐cholesterol high‐fat diet, triggered significant colonic inflammation in KO hamsters, characterized by epithelial damage, inflammatory cell infiltration, and elevated pro‐inflammatory cytokine levels. These pathological changes were associated with impaired mucosal barrier integrity, a four‐fold increase in epithelial cholesterol accumulation, and reduced E‐cadherin, ZO‐1 and occludin expression. Furthermore, ABCA1 deficiency promoted oxidative stress and induced marked remodeling of the gut microbiota. Conclusions: Our findings establish a pathogenic role for ABCA1 deficiency in driving colonic epithelial injury and inflammation, suggesting that ABCA1 may play an important role in the pathogenesis of IBD.
SN - 2096-5451
SN - 2576-2095
ER -