ORIGINAL RESEARCH article

Front. Nutr.

Sec. Nutrition and Metabolism

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1574151

This article is part of the Research TopicNutraceuticals and Functional Foods in Chronic Disease Prevention and TreatmentView all 10 articles

D-Psicose mitigates NAFLD mice induced by a high-fat diet by reducing lipid accumulation, inflammation, and oxidative stress

Provisionally accepted
Jiajun  TanJiajun Tan1Wen  SunWen Sun2雪云  董雪云 董1Jiayuan  HeJiayuan He3Asmaa  AliAsmaa Ali4Min  ChenMin Chen1Leilei  ZhangLeilei Zhang1Liang  WuLiang Wu1*Keke  ShaoKeke Shao5
  • 1Jiangsu University, Zhenjiang, China
  • 2Jurong People's Hospital, Jurong, China
  • 3Zhenjiang Center for Disease Control and Prevention, Zhenjiang, Jiangsu Province, China
  • 4Abbassia Chest Hospital, Cairo, Beni Suef, Egypt
  • 5Yancheng First People's Hospital, Yancheng, Jiangsu, China

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

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 nontargeted 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.

Keywords: D-Psicose, Non-alcoholic fatty liver disease, Oxidative Stress, Gut Microbiota, Metabolomics

Received: 10 Feb 2025; Accepted: 29 Apr 2025.

Copyright: © 2025 Tan, Sun, 董, He, Ali, Chen, Zhang, Wu and Shao. 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: Liang Wu, Jiangsu University, Zhenjiang, China

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