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- Title
Attenuation of plasma annexin A1 in human obesity.
- Authors
Kosicka, Anna; Cunliffe, Adam D.; Mackenzie, Richard; Zariwala, M. Gulrez; Perretti, Mauro; Flower, Roderick J.; Renshaw, Derek
- 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 adipocytoldne leptin, suggesting that as systemic inflammation increases, anti-inflanunatory 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
- Subjects
ANNEXINS; CALCIUM-binding proteins; FAT cells; ADIPOKINES; INFLAMMATION
- Publication
FASEB Journal, 2013, Vol 27, Issue 1, p368
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-213728