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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Main Authors: Jiajun Tan, Wen Sun, Xueyun Dong, Jiayuan He, Asmaa Ali, Min Chen, Leilei Zhang, Liang Wu, Keke Shao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
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.
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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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