Dityrosine Aggravates Hepatic Insulin Resistance in Obese Mice by Altering Gut Microbiota and the LPS/TLR4/NF-?B Inflammatory Pathway

文献类型： 外文期刊

第一作者： Ding, Yin-Yi

作者： Ding, Yin-Yi;Lan, Jinchi;Fang, Yumeng;Pan, Yuxiang;Gu, Zhenyu;Xue, Jing;Ding, Yin-Yi;Shen, Qing;Xue, Jing;Shen, Qing;Yang, Ying;Jiang, Mengqi;Ge, Yujun

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关键词： dityrosine; gut microbiota; HFD-induced obesity mice; insulin resistance; LPS/TLR4/NF-kappa B inflammatory pathway

期刊名称：MOLECULAR NUTRITION & FOOD RESEARCH （ 影响因子：5.2； 五年影响因子：6.2 ）

ISSN： 1613-4125

年卷期： 2023 年

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收录情况： SCI

摘要： Scope: Dityrosine is the main product of protein oxidation, which has been proved to be a threat to human health. This study aims to investigate whether dityrosine exacerbates insulin resistance by inducing gut flora disturbance and associated inflammatory responses. Methods and results: Mice fed with normal diet or high-fat diet (HFD) received daily gavage of dityrosine (320 mu g kg(-1) BW) or saline for consecutive 13 weeks. The effects of dityrosine on gut microbiota are verified by in vitro fermentation using fecal microbiota from db/m mice and db/db mice. As a result, dityrosine causes the insulin resistance in mice fed normal diet, and aggravates the effects of HFD on insulin sensitivity. Dityrosine increases the levels of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) but decreases levels of interleukin-10 (IL-10) in the plasma of CON and HFD-fed mice. The changes of gut flora composition caused by dityrosine are significantly correlated with the changes of inflammatory biomarkers. Conclusion: The effects of dityrosine on insulin resistance may be attributed to the reshaping of the gut microbiota composition and promoting the activity of the LPS/TLR4/NF-kappa B inflammatory pathway in HFD-induced obese individuals.

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