D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress
D-Psicose (DPS) serves as an optimal sucrose substitute, providing only 0.3% of sucrose’s energy content, while exhibiting anti-inflammatory properties and inhibiting lipid synthesis. However, its efficacy in managing non-alcoholic fatty liver disease (NAFLD) remains unclear. This study employed net...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1574151/full |
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| author | Jiajun Tan Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Asmaa Ali Min Chen Leilei Zhang Liang Wu Liang Wu Keke Shao Keke Shao |
| author_facet | Jiajun Tan Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Asmaa Ali Min Chen Leilei Zhang Liang Wu Liang Wu Keke Shao Keke Shao |
| author_sort | Jiajun Tan |
| collection | DOAJ |
| description | D-Psicose (DPS) serves as an optimal sucrose substitute, providing only 0.3% of sucrose’s energy content, while exhibiting anti-inflammatory properties and inhibiting lipid synthesis. However, its efficacy in managing non-alcoholic fatty liver disease (NAFLD) remains unclear. This study employed network pharmacology and molecular docking to identify potential DPS targets for NAFLD treatment. A high-fat diet was used to induce a NAFLD mouse model, with DPS administered in drinking water at 5% (high dose DPS group, DPSH group) and 2.5% (low dose DPS group, DPSL group) concentrations. After 12 weeks, blood lipid levels, liver lipid deposition, and inflammation were evaluated to assess the therapeutic effects of DPS. To explore its underlying mechanisms, colon contents 16S rRNA sequencing and serum untargeted metabolomics were performed. Results indicated that DPS significantly reduced lipid accumulation and inflammatory damage in the livers of NAFLD mice, improving both blood lipid profiles and oxidative stress. Network pharmacology analysis revealed that DPS primarily targets pathways associated with inflammation and oxidative stress, while molecular docking suggested its potential to inhibit the NF-κB pathway activation and the expression of the receptor for advanced glycation end-products (RAGE), findings corroborated by Western blotting. Additionally, gut microbiota and serum metabolomics analyses demonstrated that DPS improved microbiota composition by increasing the abundance of beneficial bacteria, such as Akkermansia, and restored serum metabolomic balance, enhancing anti-inflammatory and antioxidant metabolites like Tretinoin and Pyridoxamine. The non-targeted metabolomics results suggest that DPS is mediated by glutathione metabolism, arginine and proline metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism interferes with NAFLD progression. In conclusion, DPS may alleviate oxidative stress and lipid accumulation in NAFLD mice through the AGEs/RAGE/NF-κB pathway, while also ameliorating gut microbiota dysbiosis and serum metabolomic disturbances, fostering the production of anti-inflammatory and antioxidant metabolites. |
| format | Article |
| id | doaj-art-0780f64b5e0843508ab252e3315d1fd4 |
| institution | OA Journals |
| issn | 2296-861X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Nutrition |
| spelling | doaj-art-0780f64b5e0843508ab252e3315d1fd42025-08-20T02:29:09ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-05-011210.3389/fnut.2025.15741511574151D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stressJiajun Tan0Jiajun Tan1Wen Sun2Xueyun Dong3Jiayuan He4Asmaa Ali5Asmaa Ali6Min Chen7Leilei Zhang8Liang Wu9Liang Wu10Keke Shao11Keke Shao12Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Laboratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, ChinaCritical Care Medicine, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaHealth Testing Center, Zhenjiang Center for Disease Control and Prevention, Zhenjiang, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Pulmonary Medicine, Abbassia Chest Hospital, EMOH, Cairo, EgyptPublic Experiment and Service Center, Jiangsu University, Zhenjiang, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Laboratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, ChinaDepartment of Laboratory Medicine, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, ChinaMolecular Medical Research Center, Yancheng Clinical Medical College of Jiangsu University, Yancheng, ChinaD-Psicose (DPS) serves as an optimal sucrose substitute, providing only 0.3% of sucrose’s energy content, while exhibiting anti-inflammatory properties and inhibiting lipid synthesis. However, its efficacy in managing non-alcoholic fatty liver disease (NAFLD) remains unclear. This study employed network pharmacology and molecular docking to identify potential DPS targets for NAFLD treatment. A high-fat diet was used to induce a NAFLD mouse model, with DPS administered in drinking water at 5% (high dose DPS group, DPSH group) and 2.5% (low dose DPS group, DPSL group) concentrations. After 12 weeks, blood lipid levels, liver lipid deposition, and inflammation were evaluated to assess the therapeutic effects of DPS. To explore its underlying mechanisms, colon contents 16S rRNA sequencing and serum untargeted metabolomics were performed. Results indicated that DPS significantly reduced lipid accumulation and inflammatory damage in the livers of NAFLD mice, improving both blood lipid profiles and oxidative stress. Network pharmacology analysis revealed that DPS primarily targets pathways associated with inflammation and oxidative stress, while molecular docking suggested its potential to inhibit the NF-κB pathway activation and the expression of the receptor for advanced glycation end-products (RAGE), findings corroborated by Western blotting. Additionally, gut microbiota and serum metabolomics analyses demonstrated that DPS improved microbiota composition by increasing the abundance of beneficial bacteria, such as Akkermansia, and restored serum metabolomic balance, enhancing anti-inflammatory and antioxidant metabolites like Tretinoin and Pyridoxamine. The non-targeted metabolomics results suggest that DPS is mediated by glutathione metabolism, arginine and proline metabolism, unsaturated fatty acid biosynthesis, and linoleic acid metabolism interferes with NAFLD progression. In conclusion, DPS may alleviate oxidative stress and lipid accumulation in NAFLD mice through the AGEs/RAGE/NF-κB pathway, while also ameliorating gut microbiota dysbiosis and serum metabolomic disturbances, fostering the production of anti-inflammatory and antioxidant metabolites.https://www.frontiersin.org/articles/10.3389/fnut.2025.1574151/fullD-Psicosenon-alcoholic fatty liver diseaseoxidative stressgut microbiotametabolomics |
| spellingShingle | Jiajun Tan Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Asmaa Ali Min Chen Leilei Zhang Liang Wu Liang Wu Keke Shao Keke Shao D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress Frontiers in Nutrition D-Psicose non-alcoholic fatty liver disease oxidative stress gut microbiota metabolomics |
| title | D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress |
| title_full | D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress |
| title_fullStr | D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress |
| title_full_unstemmed | D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress |
| title_short | D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress |
| title_sort | d psicose mitigates nafld mice induced by a high fat diet by reducing lipid accumulation inflammation and oxidative stress |
| topic | D-Psicose non-alcoholic fatty liver disease oxidative stress gut microbiota metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1574151/full |
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