Food Safety Key Laboratory of Zhejiang Province, Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China.
Department of Clinical Laboratory, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, China.
Mol Nutr Food Res. 2023 Nov;67(22):e2300373. doi: 10.1002/mnfr.202300373. Epub 2023 Sep 19.
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.
Mice fed with normal diet or high-fat diet (HFD) received daily gavage of dityrosine (320 µg kg 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-κB), tumor necrosis factor-α (TNF-α), 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.
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-κB inflammatory pathway in HFD-induced obese individuals.
二酪氨酸是蛋白质氧化的主要产物，已被证明对人类健康构成威胁。本研究旨在探讨二酪氨酸是否通过诱导肠道菌群紊乱和相关炎症反应加重胰岛素抵抗。
正常饮食或高脂肪饮食（HFD）喂养的小鼠连续 13 周每天接受二酪氨酸（320µg kg BW）或生理盐水灌胃。使用 db/m 小鼠和 db/db 小鼠的粪便微生物群进行体外发酵来验证二酪氨酸对肠道微生物群的影响。结果表明，二酪氨酸可引起正常饮食喂养的小鼠胰岛素抵抗，并加重 HFD 对胰岛素敏感性的影响。二酪氨酸增加了正常饮食和高脂肪饮食喂养小鼠血浆中的脂多糖（LPS）、脂多糖结合蛋白（LBP）、Toll 样受体 4（TLR4）、核因子 kappa-B（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）水平，但降低了 IL-10（IL-10）水平。二酪氨酸引起的肠道菌群组成变化与炎症生物标志物的变化显著相关。
二酪氨酸对胰岛素抵抗的影响可能归因于肠道菌群组成的重塑和促进 LPS/TLR4/NF-κB 炎症途径在 HFD 诱导肥胖个体中的活性。
