2. Academic Validation
  3. Mitigation of gestational diabetes-induced endothelial dysfunction through FGF21-NRF2 pathway activation involving L-Cystine

Mitigation of gestational diabetes-induced endothelial dysfunction through FGF21-NRF2 pathway activation involving L-Cystine

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jul 1:167329. doi: 10.1016/j.bbadis.2024.167329.
Congcong Sun 1,  Linlin Wang 2,  Huiya Huang 3,  Zhenzhen Zheng 4,  Xiaomin Xu 1,  Hai Wang 5,  Kaixin Chen 5,  Xiaoqing Li 1,  Yanan Lai 5,  Hongping Zhang 4,  Maoping Chu 6,  Jianqiong Zheng 7
Affiliations

Affiliations

  • 1 Department of Scientific Research Center, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, Wenzhou, China.
  • 2 Children's Heart Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Obstetrics and Gynecology, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, Wenzhou, China.
  • 5 Department of Reproduction and Genetics, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, Wenzhou, China.
  • 6 Children's Heart Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325000, Zhejiang, Province, China.
  • 7 Department of Obstetrics and Gynecology, The Third Affiliated to Shanghai University, Wenzhou People's Hospital, Wenzhou, China. Electronic address: zjq1980120@163.com.
PMID: 38960053 DOI: 10.1016/j.bbadis.2024.167329
Abstract

Gestational diabetes mellitus (GDM) disrupts glucolipid metabolism, endangering maternal and fetal health. Despite limited research on its pathogenesis and treatments, we conducted a study using serum samples from GDM-diagnosed pregnant women. We performed metabolic Sequencing to identify key small molecule metabolites and explored their molecular interactions with FGF21. We also investigated FGF21's impact on GDM using blood samples from affected women. Our analysis revealed a novel finding: elevated levels of L-Cystine in GDM patients. Furthermore, we observed a positive correlation between L-Cystine and FGF21 levels, and found that L-Cystine induces NRF2 expression via FGF21 for a period of 96 h. Under high glucose (HG) conditions, FGF21 upregulates NRF2 and downstream genes NQO1 and EPHX1 via Akt phosphorylation induced by activation of IRS1, enhancing endothelial function. Additionally, we confirmed that levels of FGF21, L-Cystine, and endothelial function at the third trimester were effectively enhanced through appropriate exercise and diet during pregnancy in GDM patients (GDM + ED). These findings suggest FGF21 as a potential therapeutic agent for GDM, particularly in protecting endothelial cells. Moreover, elevated L-Cystine via appropriate exercise and diet might be a potential strategy to enhance FGF21's efficacy.

Keywords

Endothelial function; Fibroblast growth factor 21; Gestational diabetes mellitus; Glucolipid metabolism disorders; L-Cystine; Nuclear factor erythroid 2-related factor 2.

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