Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway
Abstract Studies have confirmed that elevated glucose levels could lead to renal fibrosis through the process of ferroptosis. Liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, is a potential treatment option for diabetes. This study aimed to examine the potential of liraglutide (LIRA) i...
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Nature Portfolio
2025-01-01
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| author | Qi Chen Ji-Xian Song Zhi Zhang Ji-Ren An Yu-Jing Gou Miao Tan Yashuo Zhao |
| author_facet | Qi Chen Ji-Xian Song Zhi Zhang Ji-Ren An Yu-Jing Gou Miao Tan Yashuo Zhao |
| author_sort | Qi Chen |
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| description | Abstract Studies have confirmed that elevated glucose levels could lead to renal fibrosis through the process of ferroptosis. Liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, is a potential treatment option for diabetes. This study aimed to examine the potential of liraglutide (LIRA) in inhibiting ferroptosis and reducing high glucose-induced renal fibrotic injury in mice, and whether the Fsp1-CoQ10-NAD(P)H signal pathway is a mechanism for this effect. In our study, we used db/db mice to simulate Type 2 diabetes mellitus (T2DM). The mice were intraperitoneally injected with LIRA (200 µg/kg/d) daily for 6 weeks. Renal function, pathologic changes, lipid peroxidation levels, iron levels, and ferroptosis were assessed. First, LIRA ameliorated renal dysfunction and fibrosis in db/db mice. Second, LIRA inhibited lipid peroxidation by up-regulating T-SOD, GSH-Px, and GSH activities as well as down-regulating the levels of 8-OHDG, MDA, LPO, 4-HNE, 12-Lox, and NOX4 in db/db mice. In addition, LIRA attenuated iron deposition by decreasing the expression of TfR1 and increasing the expression of FPN1. Meanwhile, LIRA reduced high levels of high glucose-induced cell viability decline and intracellular lipid peroxidation. Furthermore, LIRA inhibited ferroptosis by adjusting the Fsp1-CoQ10-NAD(P)H pathway in vivo and in vitro. These findings suggested that LIRA attenuated kidney fibrosis injury in db/db mice by inhibiting ferroptosis through the Fsp1-CoQ10-NAD(P)H pathway. |
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| institution | Kabale University |
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| publishDate | 2025-01-01 |
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| spelling | doaj-art-445fb2199c2642ca98a623db3e0670832025-01-12T12:22:58ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-85658-zExploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathwayQi Chen0Ji-Xian Song1Zhi Zhang2Ji-Ren An3Yu-Jing Gou4Miao Tan5Yashuo Zhao6Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineHebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineHebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineHebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineHebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineThe Fourth Affiliated Hospital of Hebei Medical UniversityHebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese MedicineAbstract Studies have confirmed that elevated glucose levels could lead to renal fibrosis through the process of ferroptosis. Liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, is a potential treatment option for diabetes. This study aimed to examine the potential of liraglutide (LIRA) in inhibiting ferroptosis and reducing high glucose-induced renal fibrotic injury in mice, and whether the Fsp1-CoQ10-NAD(P)H signal pathway is a mechanism for this effect. In our study, we used db/db mice to simulate Type 2 diabetes mellitus (T2DM). The mice were intraperitoneally injected with LIRA (200 µg/kg/d) daily for 6 weeks. Renal function, pathologic changes, lipid peroxidation levels, iron levels, and ferroptosis were assessed. First, LIRA ameliorated renal dysfunction and fibrosis in db/db mice. Second, LIRA inhibited lipid peroxidation by up-regulating T-SOD, GSH-Px, and GSH activities as well as down-regulating the levels of 8-OHDG, MDA, LPO, 4-HNE, 12-Lox, and NOX4 in db/db mice. In addition, LIRA attenuated iron deposition by decreasing the expression of TfR1 and increasing the expression of FPN1. Meanwhile, LIRA reduced high levels of high glucose-induced cell viability decline and intracellular lipid peroxidation. Furthermore, LIRA inhibited ferroptosis by adjusting the Fsp1-CoQ10-NAD(P)H pathway in vivo and in vitro. These findings suggested that LIRA attenuated kidney fibrosis injury in db/db mice by inhibiting ferroptosis through the Fsp1-CoQ10-NAD(P)H pathway.https://doi.org/10.1038/s41598-025-85658-zHigh glucoseLipid peroxidationIron overloadFsp1-CoQ10-NAD(P)H pathway |
| spellingShingle | Qi Chen Ji-Xian Song Zhi Zhang Ji-Ren An Yu-Jing Gou Miao Tan Yashuo Zhao Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway Scientific Reports High glucose Lipid peroxidation Iron overload Fsp1-CoQ10-NAD(P)H pathway |
| title | Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway |
| title_full | Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway |
| title_fullStr | Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway |
| title_full_unstemmed | Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway |
| title_short | Exploring Liraglutide’s mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway |
| title_sort | exploring liraglutide s mechanism in reducing renal fibrosis the fsp1 coq10 nad p h pathway |
| topic | High glucose Lipid peroxidation Iron overload Fsp1-CoQ10-NAD(P)H pathway |
| url | https://doi.org/10.1038/s41598-025-85658-z |
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