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.
| Original language | English |
|---|---|
| Pages (from-to) | 368-78 |
| Number of pages | 11 |
| Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Volume | 27 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2013 |
Keywords
- Adult
- Annexin A1
- Biomarkers
- C-Reactive Protein
- Cells, Cultured
- Enzyme-Linked Immunosorbent Assay
- Humans
- Inflammation Mediators
- Leptin
- Male
- Obesity
- Real-Time Polymerase Chain Reaction