Serum amyloid A impairs the antiinflammatory properties of HDL

J Clin Invest. 2016 Jan;126(1):266-81. doi: 10.1172/JCI83475. Epub 2015 Dec 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Lipoproteins, HDL
  • Reactive Oxygen Species
  • Serum Amyloid A Protein
  • Toll-Like Receptor 4
  • C-Reactive Protein
  • Silver Nitrate
  • Cholesterol