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Serum amyloid A impairs the antiinflammatory properties of HDL
- Source :
- Journal of Clinical Investigation. January 1, 2016, p266, 16 p.
- Publication Year :
- 2016
-
Abstract
- HDL from healthy humans and lean mice inhibits palmltate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgN[O.sub.3] fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgN[O.sub.3]- injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgN[O.sub.3]-injected mice. SAA-enriched HDL colocalized with cell surface-associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane.<br />Introduction HDL-cholesterol levels are reduced in obesity, especially in those individuals with features of the metabolic syndrome (1, 2). The metabolic syndrome is accompanied by adipose tissue (AT) (3, 4) [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.440400086
- Full Text :
- https://doi.org/10.1172/JCI83475