title: Macrophage-secreted factors inhibit ZAG expression and secretion by human adipocytes.
abstract: Zinc-alpha2-glycoprotein (ZAG), a novel adipokine, is downregulated in adipose tissue in obesity, a state characterized by increased adipose tissue macrophage infiltration and chronic low-grade inflammation. This study investigated whether macrophage-secreted factors and TNF-alpha, a major product of macrophages, modulate ZAG expression and secretion by human adipocytes. ZAG was produced primarily by adipocytes, and not by preadipocytes and macrophages. Incubation of preadipocytes with macrophage-conditioned medium for up to 12 days decreased ZAG mRNA and protein release, and the expression of adipogenic markers (PPARgamma and C/EBPalpha). Adipocytes treated with macrophage-conditioned medium for 24h displayed significant reductions in ZAG mRNA and release. Chronic TNF-alpha treatment let to significant decreases in ZAG expression and secretion, but marked upregulation of pro-inflammatory cytokines and chemokines (IL-6, leptin, IL-8, MCP-1 and RANTES) in adipocytes. These findings suggest that macrophage-associated inflammation may play a significant role in the downregulation of ZAG in adipose tissue in obesity.
authors.affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gao
authors.forename: P
authors.initials: P
authors.lastname: Trayhurn
authors.forename: C
authors.initials: C
authors.lastname: Bing
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D029589:Seminal Plasma Proteins / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D029589:Seminal Plasma Proteins; D014409:Tumor Necrosis Factor-alpha; D000090203:Zn-Alpha-2-Glycoprotein