{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Zinc‐α2‐glycoprotein (AZGP1), also known as ZAG, is a multifunctional secreted protein that plays a central role in lipid mobilization, energy homeostasis and tumor biology. In adipose tissue, AZGP1 is synthesized and secreted by mature adipocytes where it acts as a potent lipolytic factor—stimulating fat‐cell lipid degradation via mechanisms that include β3‐adrenoceptor activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " This lipolytic activity is thought to contribute to the pronounced adipose tissue atrophy observed in cancer cachexia, where enhanced local expression of AZGP1 has been documented."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, several studies have demonstrated that AZGP1 expression is markedly downregulated in obesity. Reduced AZGP1 synthesis in adipose tissue and liver is associated with adipocyte hypertrophy, diminished adiponectin levels and impaired insulin sensitivity. Inflammatory mediators such as TNF-α and macrophage-derived factors have been implicated in suppressing AZGP1 expression in both human and rodent models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its metabolic functions, AZGP1 has emerged as an informative biomarker in cancer. Altered tissue expression of AZGP1 has been linked to disease progression and prognosis in several tumors; for instance, lower levels in prostate and lung cancers correlate with higher tumor grade and poorer outcomes, whereas its overexpression in other cancer types is associated with metastatic behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": " In addition, physical interactions between AZGP1 and binding partners such as prolactin‐inducible protein (PIP) suggest that AZGP1 may further influence immune responses and tumor cell behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, differential AZGP1 expression has been reported in other disease contexts. Elevated levels in plasma have been proposed as a biomarker candidate for chronic pancreatitis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", while changes in tear protein profiles that include AZGP1 have been associated with ocular pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that AZGP1 serves as a key regulator of lipolysis in adipocytes and modulates systemic energy balance. Its dysregulation—whether as an upregulation in cancer cachexia or a downregulation in obesity—is closely linked to metabolic disturbances and tumor progression, thereby representing a promising target for both therapeutic intervention and biomarker development.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chen Bing, Yi Bao, John Jenkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0308647100"}], "href": "https://doi.org/10.1073/pnas.0308647100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14983038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14983038"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S T Russell, K Hirai, M J Tisdale "}, {"type": "b", "children": [{"type": "t", "text": "Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6600086"}], "href": "https://doi.org/10.1038/sj.bjc.6600086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11875710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11875710"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "T Mracek, N A Stephens, D Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6606083"}], "href": "https://doi.org/10.1038/sj.bjc.6606083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245862"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Steven Thomas Russell, Michael John Tisdale "}, {"type": "b", "children": [{"type": "t", "text": "Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2011.12.003"}], "href": "https://doi.org/10.1016/j.bbalip.2011.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22227600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22227600"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "David M Selva, Albert Lecube, Cristina Hernández, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lower zinc-alpha2-glycoprotein production by adipose tissue and liver in obese patients unrelated to insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2009-0758"}], "href": "https://doi.org/10.1210/jc.2009-0758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19622624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19622624"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "V Ceperuelo-Mallafré, S Näf, X Escoté, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating and adipose tissue gene expression of zinc-alpha2-glycoprotein in obesity: its relationship with adipokine and lipolytic gene markers in subcutaneous and visceral fat."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2009-0764"}], "href": "https://doi.org/10.1210/jc.2009-0764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19846741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19846741"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "T Mracek, D Gao, T Tzanavari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of zinc-{alpha}2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-alpha in adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/JOE-09-0299"}], "href": "https://doi.org/10.1677/JOE-09-0299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19934249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19934249"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "M P Marrades, J A Martínez, M J Moreno-Aliaga "}, {"type": "b", "children": [{"type": "t", "text": "ZAG, a lipid mobilizing adipokine, is downregulated in human obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/BF03168235"}], "href": "https://doi.org/10.1007/BF03168235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18663996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18663996"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "D Gao, P Trayhurn, C Bing "}, {"type": "b", "children": [{"type": "t", "text": "Macrophage-secreted factors inhibit ZAG expression and secretion by human adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2010.05.020"}], "href": "https://doi.org/10.1016/j.mce.2010.05.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20595026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20595026"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lourdes Garrido-Sánchez, Eduardo García-Fuentes, Diego Fernández-García, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zinc-alpha 2-glycoprotein gene expression in adipose tissue is related with insulin resistance and lipolytic genes in morbidly obese patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0033264"}], "href": "https://doi.org/10.1371/journal.pone.0033264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22442679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22442679"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Md Imtaiyaz Hassan, Abdul Waheed, Savita Yadav, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zinc alpha 2-glycoprotein: a multidisciplinary protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-07-2195"}], "href": "https://doi.org/10.1158/1541-7786.MCR-07-2195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18567794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18567794"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Aurelien Descazeaud, Alexandre de la Taille, Yves Allory, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.20405"}], "href": "https://doi.org/10.1002/pros.20405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16598739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16598739"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ligong Chang, Surong Fang, Yubao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of FASN suppresses the malignant biological behavior of non-small cell lung cancer cells via deregulating glucose metabolism and AKT/ERK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids Health Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12944-019-1058-8"}], "href": "https://doi.org/10.1186/s12944-019-1058-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31122252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31122252"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Dengbo Ji, Ming Li, Tiancheng Zhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic role of serum AZGP1, PEDF and PRDX2 in colorectal cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgt056"}], "href": "https://doi.org/10.1093/carcin/bgt056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23393224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23393224"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Daniel L Albertus, Christopher W Seder, Guoan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0b013e318189f5ec"}], "href": "https://doi.org/10.1097/JTO.0b013e318189f5ec"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18978557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18978557"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Shrestha Priyadarsini, Jesper Hjortdal, Akhee Sarker-Nag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0113310"}], "href": "https://doi.org/10.1371/journal.pone.0113310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25405607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25405607"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sheng Pan, Ru Chen, David A Crispin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr101148r"}], "href": "https://doi.org/10.1021/pr101148r"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21443201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21443201"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sivagnanam Ananthi, Namperumalsamy Venkatesh Prajna, Prajna Lalitha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathogen induced changes in the protein profile of human tears from Fusarium keratitis patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0053018"}], "href": "https://doi.org/10.1371/journal.pone.0053018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23308132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23308132"}]}]}]}