Serum amyloid A impairs the antiinflammatory properties of HDL.

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.

• Authors: Chang Yeop Han, Chongren Tang, Myriam E Guevara, Hao Wei, Tomasz Wietecha, Baohai Shao, Savitha Subramanian, Mohamed Omer, Shari Wang, Kevin D O'Brien, Santica M Marcovina, Thomas N Wight, Tomas Vaisar, Maria C de Beer, Frederick C de Beer, William R Osborne, Keith B Elkon, Alan Chait
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 126 Issue 1 Pg. 266-81 (Jan 2016) ISSN: 1558-8238 [Electronic] United States
• PMID: 26642365 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)