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Journal Article Research Support, Non-U.S. Gov't Epublish 1 citation

PubMed: 39799153 DOI: 10.1038/s41598-025-85658-z

Exploring Liraglutide's mechanism in reducing renal fibrosis: the Fsp1-CoQ10-NAD(P)H pathway.

Sci Rep 15(1):1754

Authors: Qi Chen, Ji-Xian Song, Zhi Zhang, Ji-Ren An, Yu-Jing Gou, Miao Tan, Yashuo Zhao

Affiliations

  • Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, NO.3, Luqian Xingyuan Road, Shijiazhuang, 050200, Hebei Province, China. College of Basic Medicine, Chengde Medical University, Chengde, 067000, China.
  • Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, NO.3, Luqian Xingyuan Road, Shijiazhuang, 050200, Hebei Province, China.
  • The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
  • Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine, Hebei University of Chinese Medicine, NO.3, Luqian Xingyuan Road, Shijiazhuang, 050200, Hebei Province, China.

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.

MeSH

Diabetes Mellitus, Glucagon-Like Peptide 1, Cells, Fibrosis, Nad, Ferroptosis, Natural Science Disciplines, Diabetes Mellitus, Type 2

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