Expression and Function of Zinc-α2-Glycoprotein
Zinc-α2-glycoprotein (ZAG), encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.
KeywordsZinc-α2-glycoprotein Metabolism Glucose Lipid Insulin sensitivity Neuron
This review was supported by the National Natural Science Foundation of China (81771391, 81401073), Chongqing Municipal Public Health Bureau, Chongqing People’s Municipal Government (20142026), and the Program for Innovative Research Team of Chongqing Kuanren Hospital, China.
Conflict of interest
The authors declare that there is no conflict of interest.
- 20.Balaž M, Ukropcova B, Kurdiova T, Vlcek M, Surova M, Krumpolec P, et al. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: the role of zinc-α2-glycoprotein. Adipocyte 2014, 4: 113–122.Google Scholar
- 41.Tian H, Ge C, Zhao F, Zhu M, Zhang L, Huo Q, et al. Downregulation of AZGP1 by Ikaros and histone deacetylase promotes tumor progression through the PTEN/Akt and CD44s pathways in hepatocellular carcinoma. Carcinogenesis 2017, 38: 207–217.Google Scholar
- 45.Maślińska D, Laure-Kamionowska M, Maślińska S. Crosstalk in human brain between globoid cell leucodystrophy and zinc-a-2-glycoprotein (ZAG), a biomarker of lipid catabolism. Folia Neuropathol 2013, 51: 312–318.Google Scholar
- 53.Liu X, Ou S, Xu T, Liu S, Yuan J, Huang H, et al. New differentially expressed genes and differential DNA methylation underlying refractory epilepsy. Oncotarget 2016, 7: 87402–87416.Google Scholar
- 55.Yang M, Liu R, Li S, Luo Y, Zhang Y, Zhang L, et al. Zinc-α2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: cross-sectional and interventional studies in normal subjects, insulin-resistant subjects, and subjects with newly diagnosed diabetes. Diabetes Care 2013, 36: 1074–1082.CrossRefGoogle Scholar
- 58.Takahashi S, Iizumi T, Mashima K, Abe T, Suzuki N. Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia. ASN Neuro 2014, 6. pii: 1759091414550997.Google Scholar