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Article History

Received: 3 August 2024

Accepted: 29 August 2025

First Online: 11 December 2025

Acknowledgements

: We thank D. Accili from Colombia University for profound discussion and instructive suggestions, and also thank Q. Wang, X. Wang, J. Wang and R. Liu (Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine) and X. Cheng (State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences). We thank Y. Huang, Q. Hang, and all members of the Core Facility of Basic Medical Sciences of Shanghai Jiao Tong University for their technical support. We thank X. Gao (Shanghai Profleader Biotechnology Co., China) for assisting in ultra-performance LC-MS/MS measurements of BA profiles. We thank XYZGenomics Co. for their assistance with single-cell data analysis.

: Raw data of scRNA-seq and scATAC-seq are deposited in the Gene Expression Omnibus (GEO) database under the accession number GSE241408.

: The code used in this Mendelian randomisation study is publicly available at .

: This study was funded by grants from the National Natural Science Foundation of China (92157112, 82100835, 32570728, 82570934 ) and grants from National Key Research and Development Program of China (82088102), National Key Research and Development Program of China (2022YFC2505203), Noncommunicable Chronic Diseases–National Science and Technology Major Project (2024ZD0531500, 2024ZD0531502), Innovative research team of high-level local universities in Shanghai, European Union Horizon Health project NEMESIS, Walloon Region strategic axis Fonds de la Recherche Scientifique (FRFS)–Walloon Excellence in Life Sciences and Biotechnology (WELBIO), National Fund for Scientific Research (FNRS) and the Fondation Philippe Wiener–Maurice Anspach (FWA).

: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: YG, CF and GN designed and conceptualised the study. CF, TL, YH, YL, YQ, CW, YJ, DH, TC and BL conducted experiments. CF, TL, YH, YL, CW, YJ, MC, AP, JZ and YG performed quality control. JY, YQ and CF did mouse husbandry. YG, CF, TL, BL, CW, QN, MC, JZ and GN analysed and discussed the data. CF and YG wrote the first draft of the manuscript. All the authors contributed to data interpretation, critically reviewed and edited the manuscript, and approved the final version. GN, JZ and YG had full access to all the data in the study and accept responsibility for the integrity of the data and the accuracy of the data analyses.