title: Attenuation of plasma annexin A1 in human obesity.
abstract: Obesity-related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti-inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist-to-hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute-phase protein, C-reactive protein (CRP), and the adipocytokine leptin, suggesting that as systemic inflammation increases, anti-inflammatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up-regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti-inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in human obesity.
authors.affiliation: Department of Human and Health Sciences, School of Life Sciences, University of Westminster, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kosicka
authors.forename: Adam D
authors.initials: AD
authors.lastname: Cunliffe
authors.forename: Richard
authors.initials: R
authors.lastname: Mackenzie
authors.forename: M Gulrez
authors.initials: MG
authors.lastname: Zariwala
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Flower
authors.forename: Derek
authors.initials: D
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D017305:Annexin A1 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017305:Annexin A1; D015415:Biomarkers; D018836:Inflammation Mediators; D020738:Leptin; D002097:C-Reactive Protein