Zinc-α2-Glycoprotein and Metabolic Regulation
Summary
ZAG is a 41-kDa secreted glycoprotein primarily produced by adipocytes, hepatocytes and epithelial cells. It functions as an adipokine that promotes lipid mobilisation and energy expenditure by activating lipolytic pathways, modulating glucose homeostasis and enhancing insulin sensitivity. Emerging evidence highlights its role as a counter-regulatory factor in obesity, type 2 diabetes and cachexia, with circulating and tissue levels inversely correlated with fat mass and insulin resistance. Mechanistically, ZAG interacts with the β3-adrenergic receptor to stimulate hormone-sensitive lipase and may influence PPAR-γ signalling to drive white adipose tissue browning. Its zinc-binding site further suggests a feedback relationship with zinc homeostasis, linking trace element status to metabolic control. Given its multifaceted actions, ZAG has attracted interest as both a biomarker and potential therapeutic target across metabolic disorders.
Research from Nature Portfolio
Recent studies have demonstrated that pharmacological modulation of renal glucose transport can influence circulating ZAG levels in type 2 diabetes. Treatment with an SGLT2 inhibitor over three months led to significant reductions in glycaemic indicators, body weight and fat percentage, concurrently increasing plasma ZAG and adiponectin levels. In cultured hepatocytes, the inhibitor enhanced ZAG expression and secretion via activation of PPAR-γ, an effect abrogated by a PPAR-γ antagonist. These findings suggest that SGLT2 inhibition may exert part of its insulin-sensitising benefits through up-regulation of ZAG, linking renal glucose handling to adipokine-mediated metabolic regulation.
Zinc-α2-Glycoprotein and Metabolic Regulation publication trend
The graph below shows the total number of articles in zinc-α2-glycoprotein and metabolic regulation across all publications each year (not limited to Nature Index journals).
Technical terms
Adipokine: A signalling protein secreted by fat cells that regulates energy balance and metabolism.
Hormone-sensitive lipase (HSL): An enzyme that catalyses triglyceride breakdown into free fatty acids and glycerol in adipocytes.
β3-adrenergic receptor (β3AR): A cell-surface receptor activated by catecholamines, promoting lipolysis in adipose tissue.
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR): A calculated index to estimate insulin sensitivity based on fasting glucose and insulin levels.
Peroxisome proliferator-activated receptor gamma (PPAR-γ): A nuclear receptor that regulates adipocyte differentiation, lipid storage and insulin sensitivity.
White adipose tissue (WAT) browning: The conversion of white fat cells to a thermogenic, energy-burning phenotype resembling brown adipose tissue.
References
- Effects of Weight Loss and Aerobic Exercise Training on Adi-Pose Tissue Zinc α2-Glycoprotein and Associated Genes in Obesity. Cells (2023).
- Dynamics of Serum Inflammatory Markers and Adipokines in Patients: Implications for Monitoring Abnormal Body Weight: Preliminary Research. Metabolites (2024).
- Zinc and the Innovative Zinc-α2-Glycoprotein Adipokine Play an Important Role in Lipid Metabolism: A Critical Review. Nutrients (2021).
- Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes. Scientific Reports (2016).
About these summaries
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