Amuc_1100 alleviates HFD-induced hepatic lipid accumulation via gut microbiota in zebrafish:insights from the role of intestinal 14-3-3β/α-AOA
Background Amuc_1100,the most abundant outer membrane protein of Akkermansia muciniphila,alleviates highfat diet(HFD)-induced hepatic lipid accumulation and modulates gut microbiota in fish;however,its mechanism and mediators remain unknown.Using zebrafish model,this study aims to determine the mechanism by which Amuc_1100 reduces HFD-induced hepatic lipid accumulation through modulation of gut microbiota.Methods In main study,1-month-old zebrafish were fed a low-fat diet(LFD),HFD,or HFD supplemented with 0.01%Amuc_1100(AM0.01)for 4 weeks.Body weight gain,hepatic lipid accumulation,microbial translocation,and gut microbiota composition were evaluated.In parallel,larvae at 5 d post-fertilization were fed the same diets for 7 d and analyzed by Oil Red O staining.In validation experiments,germ-free(GF)zebrafish received microbiota transplants from donor fish fed HFD or AM0.01.Antibiotics(ABS)-treated zebrafish were fed LFD,HFD,or AM0.01 for 4 weeks.Intestinal protein interacting with Amuc_1100 was identified via pull-down and co-immunoprecipitation,and its role was confirmed using protein-protein interaction(PPI)inhibitor BV02 and gene knockdown.Data were analyzed by Student''s t-test or one-way ANOVA.Results Compared with HFD group,zebrafish in AM0.01 group showed lower body weight gain,reduced hepatic lipid accumulation,and decreased microbial translocation(P<0.05).AM0.01 feeding increased Bacillus abundance while reducing Acinetobacter,Plesiomonas and Aeromonas abundances relative to HFD(P<0.05).GF zebrafish colonized with microbiota from AM0.01-fed donors showed less hepatic lipid accumulation than those receiving microbiota from HFD-fed donors(P<0.05).In contrast,ABS-treated zebrafish showed no significant difference in hepatic triacylglycerol content between HFD and AM0.01 groups(P>0.05).Using pull-down assays with intestinal proteins from LFD-fed zebrafish,we identified 14-3-3β/α-A as an interacting protein of Amuc_1100.When 14-3-3β/α-A PPI was inhibited by BV02,Amuc_1100 failed to alter the HFD-induced gut microbiota profile in 1-month-old zebrafish(P>0.05).Moreover,either BV02 treatment or 14-3-3β/α-A knockdown abolished the protective effect of Amuc_1100 against hepatic lipid accumulation in conventional and GF zebrafish(P<0.05).Conclusions Amuc_1100 reduces hepatic lipid accumulation by modulating gut microbiota through intestinal 14-3-3β/α-A,highlighting its potential as a therapeutic target.
Qianwen Ding;Ruobing Lou;Hui Liang;Yi Wang;Shangshang Tang;Jian Zhang;Yihui Du;Chao Ran;Yalin Yang;Zhen Zhang;Yuanyuan Yao;Chen Wang;Zhen Liu;Oliana Carnevali;Fengli Zhang;Zhigang Zhou
China‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of China National Collection of Livestock and Aquatic Microbes,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaNational Key Laboratory of Agricultural Microbiology,Biotechnology Research Institute,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of ChinaHunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals,Department of Biological and Environmental Engineering,Changsha University,Changsha 410022,People’s Republic of ChinaDepartment of Life and Environmental Sciences,Universita Politecnica Delle Marche,Via Brecce Bianche,Ancona 60131,ItalyDepartment of Aquaculture,Zhejiang Ocean University,Zhoushan 316000,People’s Republic of ChinaChina‑Norway Joint Lab on Fish Gastrointestinal Microbiota,Institute of Feed Research,Chinese Academy of Agricultural Sciences,Beijing 100081,People’s Republic of China
医药卫生
Amuc_1100Gut microbiotaHepatic lipid accumulationZebrafish14-3-3β/α-A
《Journal of Animal Science and Biotechnology》 2026 (4)
P.2354-2376,23
funded by National Natural Science Foundation of China(32172958,U21A20267,32330110,32503163)National Key Research and Development Program of China(2024YFD2402004)Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ZDRW202305)Central Public-interest Scientific Institution Basal Research Fund(No.610382024002)。
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