Article ; Online: Serum amyloid A impairs the antiinflammatory properties of HDL.
The Journal of clinical investigation
2016 Volume 126, Issue 1, Page(s) 266–281
Abstract: ... 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 AgNO3-injected mice ... however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here ...
| Abstract | HDL from healthy humans and lean mice inhibits palmitate-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 AgNO3 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 AgNO3-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 AgNO3-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. |
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| MeSH term(s) | 3T3-L1 Cells ; Adipocytes/metabolism ; Animals ; C-Reactive Protein/analysis ; Cholesterol/metabolism ; Humans ; Inflammation/prevention & control ; Lipoproteins, HDL/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; Serum Amyloid A Protein/physiology ; Silver Nitrate/pharmacology ; Toll-Like Receptor 4/physiology |
| Chemical Substances | Lipoproteins, HDL ; Reactive Oxygen Species ; Serum Amyloid A Protein ; Toll-Like Receptor 4 ; C-Reactive Protein (9007-41-4) ; Silver Nitrate (95IT3W8JZE) ; Cholesterol (97C5T2UQ7J) |
| Language | English |
| Publishing date | 2016-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 3067-3 |
| ISSN | 1558-8238 ; 0021-9738 |
| ISSN (online) | 1558-8238 |
| ISSN | 0021-9738 |
| DOI | 10.1172/JCI83475 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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