Chitosan lactate mitigates metabolic-associated fatty liver disease via TGR5-mediated anti-inflammatory mechanisms and the gut-hepatic-bile acid axis

IF 3.8 2区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Journal of Functional Foods Pub Date : 2025-06-27 DOI:10.1016/j.jff.2025.106946

Yiyu Lin , Weijun Lun , Yan Bai , Qishi Che , Hua Cao , Jiao Guo , Zhengquan Su

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Abstract

As a derivative of chitosan, chitosan lactate (CTL) not only maintains the good biological activity of chitosan, but also effectively improves the water-insoluble characteristics of chitosan. We used CTL to intervene in metabolic-related fatty liver disease (MAFLD) model mice, observed the effect of CTL on MAFLD mice, and detected the expression of TGR5-PKA pathway and classical inflammatory pathway-related proteins in mouse liver. The intestinal flora and bile acids of mice were further analyzed. The results showed that CTL had good therapeutic activity against MAFLD, inhibited the activation of NF-κB inflammatory pathway in liver through TGR5-PKA-IκBα-p65 and TGR5-PKA-CREB pathways, and improved the intestinal flora structure and bile acid profile of MAFLD mice. This study shows that CTL improves high-fat diet-induced liver inflammation in MAFLD mice by regulating liver inflammation pathways, intestinal flora and bile acid profiles, laying a foundation for the development of natural drugs for the treatment of MAFLD.

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壳聚糖乳酸通过tgr5介导的抗炎机制和肠-肝-胆汁酸轴减轻代谢相关的脂肪肝疾病

壳聚糖乳酸酯（CTL）作为壳聚糖的衍生物，不仅保持了壳聚糖良好的生物活性，而且有效地改善了壳聚糖的不水溶性。我们利用CTL干预代谢相关脂肪肝（metabolic-related fatty liver disease， MAFLD）模型小鼠，观察CTL对MAFLD小鼠的影响，检测小鼠肝脏中TGR5-PKA通路和经典炎症通路相关蛋白的表达。进一步分析小鼠肠道菌群和胆汁酸。结果表明，CTL对MAFLD具有良好的治疗作用，可通过tgr5 - pka - i -κB α-p65和TGR5-PKA-CREB途径抑制肝脏NF-κB炎症通路的激活，改善MAFLD小鼠肠道菌群结构和胆汁酸谱。本研究表明CTL可通过调节肝脏炎症通路、肠道菌群和胆汁酸谱改善高脂饮食诱导的MAFLD小鼠肝脏炎症，为开发治疗MAFLD的天然药物奠定基础。

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来源期刊

Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

428

审稿时长

76 days

期刊介绍： Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.