Zinc and the Innovative Zinc-α2-Glycoprotein Adipokine Play an Important Role in Lipid Metabolism: A Critical Review

Abstract

Numerous studies indicate that zinc and the new zinc-related adipokine, zinc-α2-glycoprotein (ZAG), are involved in lipid metabolism. Excess body fat lowers blood concentrations of Zn and ZAG, leading not only to the development of obesity but also to other components of the metabolic syndrome. Zinc homeostasis disorders in the body negatively affect the lipid profile and cytokine secretion. Zinc appears to be a very important ZAG homeostasis regulator. The physiological effects of ZAG are related to lipid metabolism, but studies show that ZAG also affects glucose metabolism and is linked to insulin resistance. ZAG has a zinc binding site in its structure, which may indicate that ZAG mediates the effect of zinc on lipid metabolism. The review aimed to verify the available studies on the effects of zinc and ZAG on lipid metabolism. A literature review within the scope of this research area was conducted using articles available in PubMed (including MEDLINE), Web of Science and Cochrane Library databases. An analysis of available studies has shown that zinc improves hepatic lipid metabolism and has an impact on the lipid profile. Numerous studies have found that zinc supplementation in overweight individuals significantly reduced blood levels of total cholesterol, LDL (Low-density lipoprotein)cholesterol and triglycerides, potentially reducing cardiovascular morbidity and mortality. Some results also indicate that it increases HDL-C (High-density lipoprotein) cholesterol levels. ZAG has been shown to play a significant role in reducing obesity and improving insulin sensitivity, both in experimental animal model studies and in human studies. Furthermore, ZAG at physiologically relevant concentrations increases the release of adiponectin from human adipocytes. In addition, ZAG has been shown to inhibit in vitro leptin production. Further studies are needed to provide more data on the role of zinc and zinc-α2-glycoprotein.

Impacts of Heat Stress on Rabbit Immune Function, Endocrine, Blood Biochemical Changes, Antioxidant Capacity and Production Performance, and the Potential Mitigation Strategies of Nutritional Intervention

“…The activity of more than 300 enzymes (e.g., oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases) requires zinc as substrates ( 135 ). It is also involved in the metabolism of enzymes in the body ( 136 , 137 ). Zinc is related to the antioxidant defense system, immune function and skeletal development, a low level of zinc increases the oxidative damage of membrane caused by free radicals ( 138 ).…”

Pro-Inflammatory Profile of Adipokines in Obesity Contributes to Pathogenesis, Nutritional Disorders, and Cardiovascular Risk in Chronic Kidney Disease

“…It reduces the secretion of leptin and increases the secretion of adiponectin. Thus, its low concentration contributes to the persistence of obesity [ 118 ]. At physiological concentrations, ZAG increases the expression of peroxisome proliferator-activated receptor γ (PPARγ) and early B-cell factor 2 (EBCF-2) genes by stimulating cyclic AMP (cAMP).…”

Islet Biology and Metabolism

“…Early estimates, however, report that exposure to the extracellular environment would likely dissipate the insulin-zinc hexamer seconds after complex dilution outside of the β-cell [64], allowing monomeric insulin to circulate and signal. Notably, reductions in circulating and pancreatic Zn 2+ levels are implicated in those with excess fat and T2D [254,255], and Zn 2+ supplementation can enhance insulin secretion to better control glycemia during the insulin resistant state [256]. Thus, intracellular changes in Zn 2+ could drive aspects of β-cell dysfunction.…”