TY - JOUR
T1 - The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism
AU - Liu, Chang
AU - Zheng, Xiaojiao
AU - Ji, Jian
AU - Zhu, Xuan
AU - Liu, Xiaoning
AU - Liu, He
AU - Guo, Lichun
AU - Ye, Kun
AU - Zhang, Shuang
AU - Xu, Yong-jiang
AU - Sun, Xiulan
AU - Zhou, Weibiao
AU - Wong, Hoi Leong Xavier
AU - Tian, Yaoqi
AU - Qian, He
N1 - Funding Information:
The gastrointestinal digestion and fermentation work is supported by the National Key Research and Development Program of China (No. 2021YFD2100101, Y.Q.T.). This work is also financially by National Natural Science Foundation of China (U24A20797, X.J.Z. and H.Q.), National Natural Science Foundation of China (32125031, X.L.S.), China Postdoctoral Science Foundation (2024M761182, C.L.), Postdoctoral Fellowship Program of CPSF (No. GZB20240279, C.L.), Basic Research Program of Jiangsu (Grants No. BK20241613, C.L.), and Jiangsu Funding Program for Excellent Postdoctoral Talent (No. 2024ZB209, C.L.).
Publisher Copyright:
© The Author(s) 2025.
PY - 2025/4/8
Y1 - 2025/4/8
N2 - Torularhodin, a unique carotenoid, confers beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism underlying its therapeutic effects remains unknown. Here, we report that torularhodin alleviates NAFLD in male mice by modulating the gut microbiota. Additionally, transplanting fecal microbiota from torularhodin-treated mice to germ-free mice also improves NAFLD. Mechanistically, torularhodin specifically enriches the abundance of Akkermansia muciniphila, which alleviates NAFLD by promoting the synthesis of adenosylcobalamin. Utilizing a human gastrointestinal system and a colonic organoid model, we further demonstrate that adenosylcobalamin confers protective effects against NAFLD through reducing ceramides, a well-known liver damaging compound, and this effect is mediated by inhibition of the hypoxia-inducible factor 2α pathway. Notably, we construct electrospun microsphere-encapsulated torularhodin, which facilitates the slow release of torularhodin in the colon. Together, our findings indicate the therapeutic potential of microbial utilization of carotenoids, such as torularhodin, for treating NAFLD.
AB - Torularhodin, a unique carotenoid, confers beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism underlying its therapeutic effects remains unknown. Here, we report that torularhodin alleviates NAFLD in male mice by modulating the gut microbiota. Additionally, transplanting fecal microbiota from torularhodin-treated mice to germ-free mice also improves NAFLD. Mechanistically, torularhodin specifically enriches the abundance of Akkermansia muciniphila, which alleviates NAFLD by promoting the synthesis of adenosylcobalamin. Utilizing a human gastrointestinal system and a colonic organoid model, we further demonstrate that adenosylcobalamin confers protective effects against NAFLD through reducing ceramides, a well-known liver damaging compound, and this effect is mediated by inhibition of the hypoxia-inducible factor 2α pathway. Notably, we construct electrospun microsphere-encapsulated torularhodin, which facilitates the slow release of torularhodin in the colon. Together, our findings indicate the therapeutic potential of microbial utilization of carotenoids, such as torularhodin, for treating NAFLD.
U2 - 10.1038/s41467-025-58500-3
DO - 10.1038/s41467-025-58500-3
M3 - Journal article
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
M1 - 3338
ER -
