Date on Master's Thesis/Doctoral Dissertation

12-2023

Document Type

Master's Thesis

Degree Name

M.S.

Department

Pharmacology and Toxicology

Degree Program

Pharmacology and Toxicology, MS

Committee Chair

Young-Wise, Jamie

Committee Member

Cave, Matthew

Committee Member

Wahlang, Banrida

Committee Member

Conklin, Daniel

Committee Member

Jala, Venkatakrishna

Committee Member

Merchant, Michael

Author's Keywords

Metabolic dysfunction-associated steatotic liver disease (MASLD); Zinc supplementation; high fat diet; liver injury, therapeutic agent

Abstract

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation did not change glucose handling, steatosis, or liver injury. Results from our model suggest 8-week zinc supplementation cannot reverse established MASLD. The HFD may have caused disease progression beyond rescue by the 8-week supplementation. Future studies will address these limitations, providing insights into zinc as a therapy for established MASLD.

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