open access
The new adipokine zinc-α2-glycoprotein (ZAG) as a link between adipose tissue and kidney? [Czy nowa adipocytokina cynkowa α2-glikoproteina (ZAG) stanowi ogniwo między tkanką tłuszczową a nerkami?]
Affiliations- Department of Internal Medicine, Diabetology, and Nephrology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland, Zabrze, Poland
- Department of Paediatrics, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
- Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
open access
Abstract
Adipose tissue is currently considered not only as an energy store but also as an organ of internal secretion. Numerous adipocytokines regulating a number of human body processes are important in many disease processes, including chronic kidney disease (CKD). Nowadays, the role of zinc a2-glycoprotein (ZAG) is being sought as a potential link between these two organs. ZAG, through its lipolytic effect, contributes to progressive malnutrition in patients undergoing dialysis, and this significantly increases their mortality. It seems that ZAG may be a new potential biomarker of kidney damage, and the specific pharmacotherapy will significantly reduce the progressive process of cachexia.
Abstract
Adipose tissue is currently considered not only as an energy store but also as an organ of internal secretion. Numerous adipocytokines regulating a number of human body processes are important in many disease processes, including chronic kidney disease (CKD). Nowadays, the role of zinc a2-glycoprotein (ZAG) is being sought as a potential link between these two organs. ZAG, through its lipolytic effect, contributes to progressive malnutrition in patients undergoing dialysis, and this significantly increases their mortality. It seems that ZAG may be a new potential biomarker of kidney damage, and the specific pharmacotherapy will significantly reduce the progressive process of cachexia.
Keywords
ZAG (zinc-α2-glycoprotein); malnutrition; adipose tissue; chronic kidney disease
About this articleTitle
The new adipokine zinc-α2-glycoprotein (ZAG) as a link between adipose tissue and kidney? [Czy nowa adipocytokina cynkowa α2-glikoproteina (ZAG) stanowi ogniwo między tkanką tłuszczową a nerkami?]
Journal
Issue
Article type
Review paper
Pages
171-189
Published online
2019-04-30
Page views
2424
Article views/downloads
1359
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2019;70(2):171-189.
Keywords
ZAG (zinc-α2-glycoprotein)
malnutrition
adipose tissue
chronic kidney disease
Authors
Łukasz A. Woźny
Małgorzata Morawiecka-Pietrzak
Majka Jaszczura
Katarzyna Ziora
Władysław Grzeszczak
References (40)- Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord. 2015; 13(10): 423–444.
- Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004; 92(3): 347–355.
- Burgi W, Schmid K. Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma. J Biol Chem. 1961; 236: 1066–1074.
- Kelleher SL, McCormick NH, Velasquez V, et al. Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland. Adv Nutr. 2011; 2(2): 101–111.
- Mracek T, Ding Q, Tzanavari T, et al. The adipokine zinc-alpha2-glycoprotein (ZAG) is downregulated with fat mass expansion in obesity. Clin Endocrinol (Oxf). 2010; 72(3): 334–341.
- Hassan MdI, Waheed A, Yadav S, et al. Zinc alpha 2-glycoprotein: a multidisciplinary protein. Mol Cancer Res. 2008; 6(6): 892–906.
- Fearon KCH, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012; 16(2): 153–166.
- Yip PY, Kench JG, Rasiah KK, et al. Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer. Prostate. 2011; 71(15): 1638–1645.
- Abdul-Rahman PS, Lim BK, Hashim OH. Expression of high-abundance proteins in sera of patients with endometrial and cervical cancers: analysis using 2-DE with silver staining and lectin detection methods. Electrophoresis. 2007; 28(12): 1989–1996.
- Wang Y, Li YM, Zhang S, et al. Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy. J Int Med Res. 2016; 44(2): 278–286.
- Kong B, Michalski CW, Hong X, et al. AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling. Oncogene. 2010; 29(37): 5146–5158.
- Huang Cy, Zhao Jj, Lv L, et al. Decreased expression of AZGP1 is associated with poor prognosis in primary gastric cancer. PLoS One. 2013; 8(7): e69155.
- Russell ST, Tisdale MJ. The role of glucocorticoids in the induction of zinc-alpha2-glycoprotein expression in adipose tissue in cancer cachexia. Br J Cancer. 2005; 92(5): 876–881.
- Parris TZ, Kovács A, Aziz L, et al. Additive effect of the AZGP1, PIP, S100A8 and UBE2C molecular biomarkers improves outcome prediction in breast carcinoma. Int J Cancer. 2014; 134(7): 1617–1629.
- Ding Z, Qu F, Guo W, et al. Identification of sperm forward motility-related proteins in human seminal plasma. Mol Reprod Dev. 2007; 74(9): 1124–1131.
- Tsukamoto K, Deakin JE, Graves JA, et al. Exceptionally high conservation of the MHC class I-related gene, MR1, among mammals. Immunogenetics. 2013; 65(2): 115–124.
- Bing C, Mracek T, Gao D, et al. Zinc-α2-glycoprotein: an adipokine modulator of body fat mass? Int J Obes (Lond). 2010; 34(11): 1559–1565.
- Bing C, Bao Yi, Jenkins J, et al. Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc Natl Acad Sci USA. 2004; 101(8): 2500–2505.
- Russell ST, Zimmerman TP, Domin BA, et al. Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein. Biochim Biophys Acta. 2004; 1636(1): 59–68.
- KDIGO clinical practice guideline for glomerulonephritis. Kidney Int. 2012; 2(Suppl 2): 139–274.
- Mak RH, Ikizler AT, Kovesdy CP, et al. Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle. 2011; 2(1): 9–25.
- Sikorska D, Szkudlarek M, Kłysz P, et al. Przekrojowa ocena związku między stadium przewlekłej choroby nerek a wskaźnikami przewlekłego stanu zapalnego i wybranymi wskaźnikami zmian w układzie sercowo-naczyniowym. Nowiny Lek. 2013; 82(3): 197–203.
- Beberashvili I, Sinuani I, Azar A, et al. IL-6 levels, nutritional status, and mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol. 2011; 6(9): 2253–2263.
- Stenvinkel P, Barany P, Heimbürger O, et al. Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6? Kidney Int Suppl. 2002(80): 103–108.
- Shafi T, Jaar BG, Plantinga LC, et al. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010; 56(2): 348–358.
- Barreto DV, Barreto FC, Liabeuf S. Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney Int. 2010; 77(6): 550–556.
- Amabile N, Guérin AP, Tedgui A, et al. Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. Nephrol Dial Transplant. 2012; 27(5): 1873–1880.
- Mak RH, Cheung WW, Zhan JY, et al. Cachexia and protein-energy wasting in children with chronic kidney disease. Pediatr Nephrol. 2012; 27(2): 173–181.
- Mracek T, Stephens NA, Gao D, et al. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients. Br J Cancer. 2011; 104(3): 441–447.
- Glass CK, Olefsky JM. Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab . 2012; 15(5): 635–641.
- Gołębiewska J, Lichodziejewska-Niemierko M, Rutkowski B. Miejsce octanu megestrolu w leczeniu niedożywienia u pacjentów dializowanych. Nefrol Dial Pol. 2007; 11: 66–69.
- Grabiec K, Burchert M, Milewska M, et al. Ogólnoustrojowe i miejscowe mechanizmy prowadzące do kacheksji w chorobach nowotworowych [Systemic and local mechanisms leading to cachexia in cancer]. Postępy Hig Med Dośw. 2013; 67: 1397–1409.
- Legaspi A, Jeevanandam M, Starnes HF, et al. Whole body lipid and energy metabolism in the cancer patient. Metabolism. 1987; 36(10): 958–963.
- Evans WJ. Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr. 2010; 91(4): 1123S–1127S.
- Park J, Euhus DM, Scherer PE. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev. 2011; 32(4): 550–570.
- Shibata S, Miura K. Nephritogenic glycoprotein. IX. Plasma Zn-alpha2-glycoprotein as a second source of nephritogenic glycoprotein in urine. Nephron. 1982; 31(2): 170–176.
- Wang Y, Li YM, Zhang S, et al. Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy. J Int Med Res. 2016; 44(2): 278–286.
- Lim SC, Liying DQ, Toy WC, et al. Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy. Diabet Med. 2012; 29(7): 945–949.
- Pelletier CC, Koppe L, Croze ML, et al. White adipose tissue overproduces the lipid-mobilizing factor zinc α2-glycoprotein in chronic kidney disease. Kidney Int. 2013; 83(5): 878–886.
- Leal VO, Lobo JC, Stockler-Pinto MB, et al. Is zinc-α2-glycoprotein a cardiovascular protective factor for patients undergoing hemodialysis? Clin Chim Acta. 2012; 413(5–6): 616–619.
