Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 5.
doi: 10.1007/s12011-025-04663-5. Online ahead of print.

Zinc Deficiency Aggravates High-Fat Diet-Induced Renal Injury by Regulating Oxidative Stress and Inflammation via the Nrf2/HO-1 Pathway

Yucan Guan  1 , Linlin Wu  2 , Man Wu  1 , Yuexin Zhu  1 , Ping Luo  3 , Manyu Luo  4
Affiliations

Zinc Deficiency Aggravates High-Fat Diet-Induced Renal Injury by Regulating Oxidative Stress and Inflammation via the Nrf2/HO-1 Pathway

Yucan Guan et al. Biol Trace Elem Res. .

Abstract

Obesity-related kidney disease (ORG) is associated with oxidative stress and inflammation. Zinc plays a crucial role in antioxidative defense, but its deficiency may exacerbate renal injury. The role of Zn deficiency in obesity-induced oxidative stress remains unclear. Male C57BL/6J mice were divided into four groups: ND/NZ (normal diet, normal Zn), ND/LZ (normal diet, low Zn), HFD/NZ (high-fat diet, normal Zn), and HFD/LZ (high-fat diet, low Zn) groups. After 24 weeks, renal function, histopathology, oxidative stress, and inflammatory markers were analyzed. The levels of ROS and key proteins in the Nrf2/HO-1 and PI3K/Akt pathways were assessed via Western blotting and immunofluorescence. An in vitro MPC5 podocyte model was used to examine the effects of Zn under palmitic acid stimulation, with siRNA-mediated Nrf2 knockdown. Zn deficiency exacerbated renal dysfunction, fibrosis, and inflammation in obese mice; increased ROS levels; suppressed Nrf2 signaling; and activated PI3K/Akt. In vitro, Zn supplementation reduced ROS levels and restored Nrf2 nuclear translocation, whereas Nrf2 knockdown aggravated oxidative stress. Zn deficiency promotes obesity-induced renal injury by increasing oxidative stress and inflammation through Nrf2 inhibition and PI3K/Akt activation.

Keywords: Nrf2; Obesity; Oxidative stress; PI3K/Akt; Renal inflammation; Zinc deficiency.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval: The ethics governing the use and conduct of experiments on animals were strictly observed, and the experimental protocol was approved by the Ethics Committee of the School of Basic Medical Sciences of Jilin University (No.202574). Competing Interests: The authors declare no competing interests.

Similar articles

See all similar articles

References

    1. García-Carro C, Vergara A, Bermejo S, Azancot MA, Sellarés J, Soler MJ (2021) A Nephrologist Perspective on Obesity: From Kidney Injury to Clinical Management. Front Med (Lausanne). 8:655871. https://doi.org/10.3389/fmed.2021.655871 - DOI - PubMed - PMC
    1. Choi S, Liu X, Pan Z (2018) Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases. Acta Pharmacol Sin 39:1120–1132. https://doi.org/10.1038/aps.2018.25 - DOI - PubMed - PMC
    1. Câmara NO, Iseki K, Kramer H, Liu ZH, Sharma K (2017) Kidney disease and obesity: epidemiology, mechanisms and treatment. Nat Rev Nephrol 13:181–190. https://doi.org/10.1038/nrneph.2016.191 - DOI - PubMed
    1. Sun Y, Ge X, Li X, He J, Wei X, Du J, Sun J, Li X, Xun Z, Liu W, Zhang H, Wang ZY, Li YC (2020) High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction. Cell Death Dis. 11:914. https://doi.org/10.1038/s41419-020-03122-4 - DOI - PubMed - PMC
    1. Pérez-Torres I, Castrejón-Téllez V, Soto ME, Rubio-Ruiz ME, Manzano-Pech L, Guarner-Lans V (2021) Oxidative stress plant natural antioxidants and obesity. Int J Mol Sci 22:1786. https://doi.org/10.3390/ijms22041786 - DOI - PubMed - PMC

LinkOut - more resources