The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism

Chang Liu, Xiaojiao Zheng, Jian Ji, Xuan Zhu, Xiaoning Liu, He Liu, Lichun Guo, Kun Ye, Shuang Zhang, Yong-jiang Xu, Xiulan Sun, Weibiao Zhou, Hoi Leong Xavier Wong (), Yaoqi Tian () and He Qian ()
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Chang Liu: Jiangnan University
Xiaojiao Zheng: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jian Ji: Jiangnan University
Xuan Zhu: Zhejiang Gongshang University
Xiaoning Liu: Agency for Science Technology and Research
He Liu: Zhejiang University
Lichun Guo: Jiangnan University
Kun Ye: ETH Zürich
Shuang Zhang: Jiangnan University
Yong-jiang Xu: Jiangnan University
Xiulan Sun: Jiangnan University
Weibiao Zhou: National University of Singapore
Hoi Leong Xavier Wong: Hong Kong Baptist University
Yaoqi Tian: Jiangnan University
He Qian: Jiangnan University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58500-3

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