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烟酸联合上调GPR109A减轻酒精性脂肪肝疾病的调控机制研究

Study on the Regulatory Mechanism of Niacin Combined with in Alleviating Alcoholic Fatty Liver Disease by Up-Regulating GPR109A.

作者信息

Liang Xi, Shan Tianhu, Zheng Xiumei, Zhang Zhe, Fan Yanping, Zhang Huaqi, Zhang Lanwei, Liang Hui

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Qingdao University, 308 Ningxia Road, Qingdao 266071, China.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.

出版信息

Nutrients. 2024 Nov 30;16(23):4170. doi: 10.3390/nu16234170.

Abstract

BACKGROUND

This study aimed to investigate the effects of niacin combined with F1-7 on the improvement of alcoholic fatty liver disease (AFLD) in mice and its potential regulatory mechanism.

METHODS

A total of 75 8-week-old male C57BL/6N mice were acclimated for one week and randomly divided into five groups: control group, alcohol model group (AFLD), niacin intervention group (NA), F1-7 intervention group (F1-7), and niacin combined with F1-7 intervention group (NF). The experiment lasted for 8 weeks.

RESULTS

The results showed that all intervention groups could effectively reduce the serum lipid levels and inflammatory response of mice induced by alcohol to varying degrees. The immunofluorescence analysis showed that the GPR109A in the liver and intestine of the NF group was significantly enhanced compared with the other groups. Niacin combined with F1-7 better restored the gut microbiota. Meanwhile, each intervention group could increase their levels of SCFAs. Among them, the combination group increased the levels of acetic acid and butyric acid more significantly than the other two groups. The Spearman's correlation analysis of gut microbiota and SCFAs showed that , , and were positively correlated with changes in SCFAs, while , , and were negatively correlated.

CONCLUSIONS

Niacin combined with F1-7 better regulated the gut microbial balance and increased the SCFAs in mice with alcoholic steatohepatitis. The mechanism was related to the activation of the target GPR109A, which regulates the key proteins involved in lipid synthesis and -oxidation to improve lipid metabolic disorders.

摘要

背景

本研究旨在探讨烟酸联合F1-7对改善小鼠酒精性脂肪性肝病(AFLD)的作用及其潜在调控机制。

方法

将75只8周龄雄性C57BL/6N小鼠适应性饲养1周后,随机分为五组:对照组、酒精模型组(AFLD)、烟酸干预组(NA)、F1-7干预组(F1-7)、烟酸联合F1-7干预组(NF)。实验持续8周。

结果

结果显示,各干预组均能不同程度有效降低酒精诱导的小鼠血脂水平和炎症反应。免疫荧光分析表明,与其他组相比,NF组肝脏和肠道中的GPR109A显著增强。烟酸联合F1-7能更好地恢复肠道微生物群。同时,各干预组均可提高短链脂肪酸水平。其中,联合组乙酸和丁酸水平升高幅度明显大于其他两组。肠道微生物群与短链脂肪酸的Spearman相关性分析表明, 、 、 与短链脂肪酸变化呈正相关,而 、 、 与短链脂肪酸变化呈负相关。

结论

烟酸联合F1-7能更好地调节酒精性脂肪性肝炎小鼠的肠道微生物平衡,增加短链脂肪酸。其机制与激活靶标GPR109A有关,GPR109A调节参与脂质合成和β-氧化的关键蛋白,以改善脂质代谢紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f16/11644097/d7a1b76f899c/nutrients-16-04170-g001.jpg

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