NRF2/HO-1 axis regulates fructose-induced lipid accumulation in hepatocytes
Redox Experimental Medicine, vol.2026, no.1, 2026 (ESCI, Scopus)
- Publication Type: Article / Article
- Volume: 2026 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1530/rem-26-0004
- Journal Name: Redox Experimental Medicine
- Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus
- Keywords: fructose, HO-1, lipid droplet, NRF2
- Acibadem Mehmet Ali Aydinlar University Affiliated: Yes
Abstract
Objective: Nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor involved in redox homeostasis, plays a critical role in preventing lipid peroxidation against various hepatic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD). Growing body of evidence suggests that excessive fructose consumption contributes to hepatic lipid accumulation. Methods: Lipid accumulation in hepatocytes was induced by fructose treatment, while small interfering RNA (siRNA) transfection was used to suppress sterol regulatory element-binding protein-1c (SREBP-1c) expression. The size and the number of lipid droplets (LDs), as well as nuclear translocation of NRF2, were evaluated using microscopic analysis. Protein and mRNA expression levels were assessed by western blotting and qRT-PCR, respectively. Oxidative stress was analyzed using flow cytometry. Results: Fructose administration significantly increased LD accumulation and oxidative stress, accompanied by NRF2 activation and SREBP-1c expression. Silencing of SREBP-1c in fructose-treated hepatocytes markedly reduced LD accumulation and attenuated activation of the NRF2 signaling pathway. In contrast, inhibition of heme oxygenase-1 (HO-1) partially reversed these effects. Conclusion: The NRF2/HO-1 axis is involved in cellular adaptive response to fructose-induced oxidative stress and excessive LD accumulation. Significance statement Elucidating the involvement of the NRF2/HO-1 axis between fructose metabolism and LD accumulation may provide valuable insights for the development of therapeutic strategies targeting fatty liver disorders.