title: 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.forename: Chang Yeop
authors.initials: CY
authors.lastname: Han
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Myriam E
authors.initials: ME
authors.lastname: Guevara
authors.forename: Hao
authors.initials: H
authors.lastname: Wei
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wietecha
authors.forename: Baohai
authors.initials: B
authors.lastname: Shao
authors.forename: Savitha
authors.initials: S
authors.lastname: Subramanian
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omer
authors.forename: Shari
authors.initials: S
authors.lastname: Wang
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.forename: Maria C
authors.initials: MC
authors.lastname: de Beer
authors.forename: Frederick C
authors.initials: FC
authors.lastname: de Beer
authors.forename: William R
authors.initials: WR
authors.lastname: Osborne
authors.forename: Keith B
authors.initials: KB
authors.lastname: Elkon
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008075:Lipoproteins, HDL / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017382:Reactive Oxygen Species / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000502:physiology*; D012835:Silver Nitrate / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D008075:Lipoproteins, HDL; D017382:Reactive Oxygen Species; D000685:Serum Amyloid A Protein; D051197:Toll-Like Receptor 4; D002097:C-Reactive Protein; D012835:Silver Nitrate; D002784:Cholesterol