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

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.

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Publication Details

Journal
Nature Communications
Published
2025-04-08
DOI
https://doi.org/10.1038/s41467-025-58500-3
Citations
18
Primary Topic
Folate and B Vitamins Research
Type
article
Field-Weighted Citation Impact
30.03

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article

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

Hoi Leong Xavier Wong, Weibiao Zhou, Xuan Zhu, Lichun Guo et al.
18 citations
Nature Communications
Folate and B Vitamins Research
30.03
article

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

Hoi Leong Xavier Wong, Weibiao Zhou, Xuan Zhu, Lichun Guo, Xiulan Sun, Shuang Zhang, Yaoqi Tian, Chang Liu, Yong‐Jiang Xu, He Qian, Xiaoning Liu, Xiaojiao Zheng, Jian Ji, Kun Ye, Liu He
article en
18 citations

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.

Nature CommunicationsVol. 16(1)
Jiangnan University (CN), Agency for Science, Technology and Research (SG), Hong Kong Baptist University (HK), National University of Singapore (SG), Shanghai Jiao Tong University (CN), Sir Run Run Shaw Hospital (CN), ETH Zurich (CH), Analysis and Testing Centre (CN), Suzhou Research Institute (CN), Shanghai Sixth People's Hospital (CN), State Key Laboratory of Food Science and Technology (CN), Zhejiang Gongshang University (CN), Institute of Molecular and Cell Biology (SG), Zhejiang University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, National Key Research and Development Program of China
Zero hunger
Openalex Percentile: Top 0%
Folate and B Vitamins Research
30.03
DOIOpen Access PDFOpenAlex
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