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Article

Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease?

by
Oluwanifemi Esther Bolatimi
1,
Kimberly Z. Head
2,3,
Jianzhu Luo
2,
Tyler C. Gripshover
1,2,4,
Qian Lin
5,
Ngozi V. Adiele
1,
Walter H. Watson
1,2,
Caitlin Wilkerson
1,
Lu Cai
1,5,6,
Matthew C. Cave
1,2,3,4,6,7,8,* and
Jamie L. Young
1,6,*
1
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40202, USA
2
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA
3
Hepatobiology & Toxicology COBRE, School of Medicine, University of Louisville, Louisville, KY 40202, USA
4
Superfund Research Program, University of Louisville, Louisville, KY 40202, USA
5
Pediatric Research Institute, Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40202, USA
6
The Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, USA
7
Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA
8
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(2), 1763; https://doi.org/10.3390/ijms24021763
Submission received: 31 December 2022 / Revised: 9 January 2023 / Accepted: 10 January 2023 / Published: 16 January 2023
(This article belongs to the Special Issue Current Topics in Trace Element and Mineral Research)
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Abstract

The pathogenesis of non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease, is associated with zinc deficiency. Previous studies show zinc supplementation improves steatosis and glucose metabolism, but its therapeutic effects in patients with established NAFLD remain unclear. We developed an in vivo model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced NAFLD and hypothesized that the established NAFLD would be attenuated by zinc supplementation. Male C57BL/6J mice were fed a control diet or HFD for 12 weeks. Mice were then further grouped into normal and zinc-supplemented diets for 8 additional weeks. Body composition and glucose tolerance were determined before and after zinc supplementation. At euthanasia, plasma and liver tissue were collected for characterization and downstream analysis. As expected, 12 weeks of HFD resulted in reduced glucose clearance and altered body composition. Eight weeks of subsequent zinc supplementation did not alter glucose handling, plasma transaminases, steatosis, or hepatic gene expression. Results from our model suggest 8-week zinc supplementation cannot reverse established NAFLD. The HFD may have caused NAFLD disease progression beyond rescue by an 8-week period of zinc supplementation. Future studies will address these limitations and provide insights into zinc as a therapeutic agent for established NAFLD.
Keywords: non-alcoholic fatty liver disease (NAFLD); high fat diet; liver injury; essential micronutrient; zinc supplementation; therapeutic agent non-alcoholic fatty liver disease (NAFLD); high fat diet; liver injury; essential micronutrient; zinc supplementation; therapeutic agent

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MDPI and ACS Style

Bolatimi, O.E.; Head, K.Z.; Luo, J.; Gripshover, T.C.; Lin, Q.; Adiele, N.V.; Watson, W.H.; Wilkerson, C.; Cai, L.; Cave, M.C.; et al. Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease? Int. J. Mol. Sci. 2023, 24, 1763. https://doi.org/10.3390/ijms24021763

AMA Style

Bolatimi OE, Head KZ, Luo J, Gripshover TC, Lin Q, Adiele NV, Watson WH, Wilkerson C, Cai L, Cave MC, et al. Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease? International Journal of Molecular Sciences. 2023; 24(2):1763. https://doi.org/10.3390/ijms24021763

Chicago/Turabian Style

Bolatimi, Oluwanifemi Esther, Kimberly Z. Head, Jianzhu Luo, Tyler C. Gripshover, Qian Lin, Ngozi V. Adiele, Walter H. Watson, Caitlin Wilkerson, Lu Cai, Matthew C. Cave, and et al. 2023. "Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease?" International Journal of Molecular Sciences 24, no. 2: 1763. https://doi.org/10.3390/ijms24021763

APA Style

Bolatimi, O. E., Head, K. Z., Luo, J., Gripshover, T. C., Lin, Q., Adiele, N. V., Watson, W. H., Wilkerson, C., Cai, L., Cave, M. C., & Young, J. L. (2023). Can Zinc Supplementation Attenuate High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease? International Journal of Molecular Sciences, 24(2), 1763. https://doi.org/10.3390/ijms24021763

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