HFD Exacerbates Hepatic Lipid Metabolism Disorders After Cholecystectomy by Regulating the Bile Acid and Neutrophil Recruitment

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-06-27 DOI:10.1111/liv.70130

Yanting Xu, Feng Zhang, Ziliang Ke, Yiken Lin, Yang Zhang, Yun Liu, Yifan Zhang, Jun Xu, Yulan Liu

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Abstract

Background and Aims

Previous studies have suggested that cholecystectomy may lead to an elevated risk of metabolic dysfunction-associated fatty liver disease (MAFLD). However, there is a dearth of knowledge concerning the precise effects and underlying mechanisms through which cholecystectomy influences hepatic lipid metabolism, necessitating further investigation.

Methods

Post-cholecystectomy (PC) model mice were established under both normal and high-fat diet conditions. Liver lipid metabolism, inflammation, bile acid profiles, and immune cell alterations were evaluated. Hepatocytes mimicking a high-fat state were exposed to distinctive bile acids to investigate the chemotactic effect on neutrophils. Co-culture experiments of hepatocytes and neutrophils evaluated lipid accumulation in hepatocytes and the expression levels of lipid metabolism-related genes.

Results

Cholecystectomy under a high-fat diet markedly disrupted hepatic lipid metabolism and exacerbated inflammation, while cholecystectomy under a normal diet did not. The bile acid profiles in the ileum and liver of PC mice underwent notable changes, along with modifications in bile acid receptors and transporters associated with enterohepatic circulation. Notably, deoxycholic acid (DCA) and tauroursodeoxycholic acid (TDCA) were identified as distinctive bile acids. Furthermore, hepatocytes in PC mice with a high-fat diet showed an elevated level of neutrophil infiltration. Hepatocytes showed a significant increase in releasing CXCL1 and CXCL2 when administered with DCA or TDCA, suggesting an intensified chemotactic response for neutrophils. Co-culturing neutrophils and hepatocytes exacerbated hepatocyte lipid deposition and reduced the expression of genes associated with lipid oxidative degradation.

Conclusions

Cholecystectomy alongside a high-fat diet aggravates hepatic lipid metabolism disorders and inflammation by modulating hepatic bile acid profiles and promoting neutrophil recruitment.

Abstract Image

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HFD通过调节胆汁酸和中性粒细胞募集加剧胆囊切除术后肝脏脂质代谢紊乱

背景和目的先前的研究表明，胆囊切除术可能导致代谢功能障碍相关脂肪性肝病（MAFLD）的风险升高。然而，关于胆囊切除术影响肝脏脂质代谢的确切作用和潜在机制的知识缺乏，需要进一步研究。方法建立正常和高脂饮食条件下的胆囊切除术后小鼠模型。评估肝脏脂质代谢、炎症、胆汁酸谱和免疫细胞改变。模拟高脂肪状态的肝细胞暴露于不同的胆汁酸中，以研究对中性粒细胞的趋化作用。肝细胞和中性粒细胞的共培养实验评估了肝细胞中的脂质积累和脂质代谢相关基因的表达水平。结果高脂饮食下的胆囊切除术明显破坏了肝脏脂质代谢并加重了炎症，而正常饮食下的胆囊切除术则没有。PC小鼠回肠和肝脏的胆汁酸谱发生了显著变化，与肠肝循环相关的胆汁酸受体和转运蛋白也发生了改变。值得注意的是，去氧胆酸（DCA）和牛磺酸去氧胆酸（TDCA）被确定为独特的胆汁酸。此外，高脂肪饮食的PC小鼠肝细胞显示中性粒细胞浸润水平升高。肝细胞在给予DCA或TDCA时，CXCL1和CXCL2的释放显著增加，表明中性粒细胞的趋化反应增强。中性粒细胞与肝细胞共培养可加重肝细胞脂质沉积，降低脂质氧化降解相关基因的表达。结论：胆囊切除术和高脂肪饮食通过调节肝胆酸谱和促进中性粒细胞募集，加重肝脂质代谢紊乱和炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.