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.
Document Type
Article
Publication Date
1-4-2016
Digital Object Identifier (DOI)
https://doi.org/10.1172/JCI83475
Funding Information
This work was supported in part by NIH grants HL092969, 094352, and DK-035816 and a Beginning Grant-in-Aid from the American Heart Association (to C.Y. Han). A. Chait was supported by a Grant-in-Aid from the American Heart Association.
Repository Citation
Han, Chang Yeop; Tang, Chongren; Guevara, Myriam E.; Wei, Hao; Wietecha, Tomasz; Shao, Baohai; Subramanian, Savitha; Omer, Mohamed; Wang, Shari; O'Brien, Kevin D.; Marcovina, Santica M.; Wight, Thomas N.; Vaisar, Tomas; de Beer, Maria C.; de Beer, Frederick C.; Osborne, William R.; Elkon, Keith B.; and Chait, Alan, "Serum Amyloid A Impairs the Antiinflammatory Properties of HDL" (2016). Physiology Faculty Publications. 91.
https://uknowledge.uky.edu/physiology_facpub/91
Notes/Citation Information
Published in The Journal of Clinical Investigation, v. 126, no. 1, p. 266-281.
Copyright © 2016, American Society for Clinical Investigation
The copyright holders have granted the permission for posting the article here.
A corrigendum was issued by the journal in Feb. 2016 and is available for download as an additional file listed below.