The association of the adipokine zinc-alpha2-glycoprotein with non-alcoholic fatty liver disease and related risk factors: A comprehensive systematic review.

BACKGROUND AND AIM The adipokine zinc-alpha2-glycoprotein (ZAG), a multidisciplinary protein, is involved in lipid metabolism, glucose homeostasis and energy balance. Accumulating evidence demonstrates that the expression of ZAG is mainly downregulated in obesity and obesity-related conditions. In the present study, we assessed the association of ZAG with non-alcoholic fatty liver disease (NAFLD) and the related risk factors including obesity, metabolic factors and inflammatory parameters, with emphasis on potential mechanisms underlying these associations. METHODS PRISMA guidelines were followed in this review. Systematic searches were performed using the PubMed/Medline, ScienceDirect, Scopus, EMBASE, ProQuest and Google Scholar databases, up to August 2020 for all relevant published papers. RESULTS Out of 362 records screened, 34 articles were included in the final analysis. According to the studies reviewed here, ZAG appears to exert a protective effect against NAFLD by enhancing mRNA expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ, promoting mRNA expression levels of the lipolysis-related genes, reducing mRNA expression levels of the lipogenesis-related genes, increasing hepatic fatty acid oxidation, ameliorating hepatic steatosis, promoting the activity of brown adipose tissue and the expression of thermogenesis-related genes, modulating energy balance and glucose homeostasis, and elevating plasma levels of healthy adipokines such as adiponectin. ZAG can also be involved in the regulation of inflammatory responses by attenuation of the expression of pro-inflammatory and pro-fibrotic mediators. CONCLUSION According to the studies reviewed here, ZAG is suggested to be a promising therapeutic target for NAFLD. However, the favourable effects of ZAG need to be confirmed in prospective cohort studies.