The adipokine zinc-α2-glycoprotein (ZAG) is downregulated with fat mass expansion in obesity

P>Introduction Zinc-alpha 2-glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes. Methods Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real-time PCR and protein by Western blotting. Results In human subjects, ZAG mRNA level was negatively correlated with BMI (r = -0 center dot 61, P < 0 center dot 001, n = 23, visceral; r = -0 center dot 6, P < 0 center dot 05, n = 14, subcutaneous) and fat mass (r = -0 center dot 62, P < 0 center dot 01, visceral; r = -0 center dot 6, P < 0 center dot 05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = -0 center dot 65, P < 0 center dot 001, visceral; r = -0 center dot 55, P < 0 center dot 05, subcutaneous) and homeostasis model of insulin resistance (HOMA-IR) (r = -0 center dot 65, P < 0 center dot 001, visceral; r = -0 center dot 52, P = 0 center dot 055, subcutaneous), and C reactive protein (CRP) (r = -0 center dot 46, P < 0 center dot 05, visceral; r = -0 center dot 53, P < 0 center dot 05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0 center dot 5, P < 0 center dot 05, visceral; r = 0 center dot 82, P < 0 center dot 001, subcutaneous) but negatively associated with leptin mRNA (r = -0 center dot 42, P < 0 center dot 05, visceral; r = -0 center dot 54, P < 0 center dot 05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes. Conclusion ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity-related insulin resistance.