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

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.

Marginal Zinc Deficiency Promotes Pancreatic Islet Enlargement While Zinc Supplementation Improves the Pancreatic Insulin Response in Zucker Diabetic Fatty Rats

“…Serum zinc concentrations are reduced in patients with non-alcoholic fatty liver disease [47] and there may be an association of lower serum zinc and greater severity of non-alcoholic fatty liver disease in humans [48,49]. However, in the present study, neither marginal Zn deficiency nor Zn supplementation altered the relative liver weight or the hepatic triglyceride levels of ZDF rats, and similarly others have reported that zinc supplementation did not alter the hepatic steatosis score of mice fed high-fat diets [50]. Dyslipidemia, especially low HDL-cholesterol and elevated triglycerides, is a common feature of type 2 diabetes in humans [2].…”

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

“…One of the important mechanisms by which zinc deficiency leads to disturbed protein metabolism in patients with chronic liver disease is diminished ammonia metabolism, which may potentially induce or exacerbate endoplasmic reticulum stress and apoptosis, thereby triggering MAFLD [237,241]. Zinc supplementation attenuates high-fat diet-induced hepatic steatosis and liver injury, which is achieved partly by improving glucose-lipid metabolism disorders, but zinc intervention cannot alleviate MAFLD caused by a high-fat diet [242,243]. Nonetheless, a randomized clinical trial observed elevated zinc levels and reduced hepatic enzyme levels in serum after zinc supplementation in patients with overweight/obesity and MAFLD [244].…”