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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1521416

Identification of Retinol Dehydrogenase 10 as a Shared Biomarker for Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes Mellitus

Provisionally accepted
Fangyu Li Fangyu Li Rui Li Rui Li *Hongjun Deng Hongjun Deng *
  • Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

The final, formatted version of the article will be published soon.

    Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for type 2 diabetes mellitus (T2DM), and its early identification and intervention offer opportunities for reversing diabetes mellitus.In this study, we identified biomarkers for the MASLD dataset (GSE33814, GSE48452) and the T2DM dataset (GSE76895 and GSE89120) by bioinformatics analysis. Next, we constructed weighted gene co-expression network (WGCNA) for disease module analysis to screen out shared genes strongly associated with diseases.We also analyzed the enriched pathways of shared genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Next, hub gene validation was performed using the least absolute shrinkage and selection operator (LASSO) and receiver operating characteristic (ROC) curves. Finally, we used RT-qPCR, immunofluorescence, western blotting and Elisa to validate hub gene expression in MASLD and T2DM mouse models.Results: This analysis identified 20 genes shared by MASLD and T2DM that were enriched in the bile secretion, phototransduction, cancer, carbohydrate digestion and absorption, cholesterol/glycerol metabolism, and retinol metabolism. The LASSO algorithm and ROC curve identified Retinol Dehydrogenase 10 (RDH10) as the best diagnostic gene for MASLD and T2DM. Immunofluorescence and Western blot showed that RDH10 expression was reduced in the liver and pancreatic islets of MASLD and T2DM model mice. Similarly, serum levels of RDH10 were significantly lower in MASLD and T2DM model mice and humans than in controls.Our study suggests that RDH10 is a common diagnostic marker for MASLD and T2DM and provides new research directions for the prevention and treatment of MASLD and T2DM.

    Keywords: Retinol dehydrogenase10, MASLD, T2DM, bioinformatics, biomarker

    Received: 01 Nov 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Li, Li and Deng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Rui Li, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Hongjun Deng, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.