A High-Fat High-Fructose Diet Dysregulates the Homeostatic Crosstalk Between Gut Microbiome, Metabolome, and Immunity in an Experimental Model of Obesity

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Molecular Nutrition & Food Research Pub Date : 2022-01-24 DOI:10.1002/mnfr.202100950

Kun-Ping Li, Min Yuan, Yong-Lin Wu, Miguel Pineda, Chu-Mei Zhang, Yan-Fen Chen, Zhi-quan Chen, Xiang-Lu Rong, Jeremy E. Turnbull, Jiao Guo

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引用次数: 13

Abstract

Scope

Ample evidence supports the prominent role of gut-liver axis in perpetuating pathological networks of high-fat high-fructose (HFF) diet induced metabolic disorders, however, the molecular mechanisms are still not fully understood. Herein, this study aims to present a holistic delineation and scientific explanation for the crosstalk between the gut and liver, including the potential mediators involved in orchestrating the metabolic and immune systems.

Methods and Results

An experimental obesity-associated metaflammation rat model is induced with a HFF diet. An integrative multi-omics analysis is then performed. Following the clues illustrated by the multi-omics discoveries, putative pathways are subsequently validated by RT-qPCR and Western blotting.

HFF diet leads to obese phenotypes in rats, as well as histopathological changes. Integrated omics analysis shows that there exists a strong interdependence among gut microbiota composition, intestinal metabolites, and innate immunity regulation in the liver. Some carboxylic acids may contribute to gut-liver communication. Moreover, activation of the hepatic LPS-TLR4 pathway in obesity is confirmed.

Conclusion

HFF-intake disturbs gut flora homeostasis. Crosstalk between gut microbiota and innate immune system mediates hepatic metaflammation in obese rats, associated with LPS-TLR4 signaling pathway activation. Moreover, α-hydroxyisobutyric acid and some other organic acids may play a role as messengers in the liver-gut axis.

Abstract Image

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在肥胖实验模型中，高脂肪高果糖饮食失调了肠道微生物组、代谢组和免疫之间的稳态串扰

大量证据支持肠-肝轴在高脂肪高果糖饮食引起的代谢紊乱的病理网络中发挥重要作用，然而，其分子机制仍未完全了解。在此，本研究旨在全面描述和科学解释肠道和肝脏之间的相互作用，包括参与协调代谢和免疫系统的潜在介质。方法与结果采用HFF饮食诱导肥胖相关性炎症模型大鼠。然后进行综合多组学分析。根据多组学发现的线索，随后通过RT-qPCR和Western blotting验证了假定的途径。HFF饮食导致大鼠肥胖表型，以及组织病理学改变。综合组学分析显示，肠道菌群组成、肠道代谢物和肝脏先天免疫调节之间存在很强的相互依赖性。一些羧酸可能有助于肠肝之间的交流。此外，肝脏LPS-TLR4通路的激活在肥胖中得到证实。结论hff摄入扰乱肠道菌群稳态。肠道微生物群与先天免疫系统之间的串扰介导肥胖大鼠肝脏炎症，与LPS-TLR4信号通路激活有关。α-羟基异丁酸和其他有机酸可能在肝肠轴中起信使作用。

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

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.