title: Apolipoprotein AI and high-density lipoprotein have anti-inflammatory effects on adipocytes via cholesterol transporters: ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1.
abstract: BACKGROUND
  Macrophage accumulation in adipose tissue associates with insulin resistance and increased cardiovascular disease risk. We previously have shown that generation of reactive oxygen species and monocyte chemotactic factors after exposure of adipocytes to saturated fatty acids, such as palmitate, occurs via translocation of NADPH oxidase 4 into lipid rafts (LRs). The anti-inflammatory effects of apolipoprotein AI (apoAI) and high-density lipoprotein (HDL) on macrophages and endothelial cells seem to occur via cholesterol depletion of LRs. However, little is known concerning anti-inflammatory effects of HDL and apoAI on adipocytes.
  
  
  OBJECTIVE
  To determine whether apoAI and HDL inhibit inflammation in adipocytes and adipose tissue, and whether this is dependent on LRs.
  
  
  RESULTS
  In 3T3L-1 adipocytes, apoAI, HDL, and methyl-β-cyclodextrin inhibited chemotactic factor expression. ApoAI and HDL also disrupted LRs, reduced plasma membrane cholesterol content, inhibited NADPH oxidase 4 translocation into LRs, and reduced palmitate-induced reactive oxygen species generation and monocyte chemotactic factor expression. Silencing ATP-binding cassette A-1 abrogated the effect of apoAI, but not HDL, whereas silencing ATP-binding cassette G-1 or scavenger receptor B-1 abrogated the effect of HDL but not apoAI. In vivo, apoAI transgenic mice fed a high-fat, high-sucrose, cholesterol-containing diet showed reduced chemotactic factor and proinflammatory cytokine expression and reduced macrophage accumulation in adipose tissue.
  
  
  CONCLUSIONS
  ApoAI and HDL have anti-inflammatory effects in adipocytes and adipose tissue similar to their effects in other cell types. These effects are consistent with disruption and removal of cholesterol from LRs, which are regulated by cholesterol transporters, such as ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1.
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98195, USA.
authors.forename: Tomio
authors.initials: T
authors.lastname: Umemoto
authors.forename: Chang Yeop
authors.initials: CY
authors.lastname: Han
authors.forename: Poulami
authors.initials: P
authors.lastname: Mitra
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Averill
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: Leela
authors.initials: L
authors.lastname: Goodspeed
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omer
authors.forename: Savitha
authors.initials: S
authors.lastname: Subramanian
authors.forename: Shari
authors.initials: S
authors.lastname: Wang
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Den Hartigh
authors.forename: Hao
authors.initials: H
authors.lastname: Wei
authors.forename: Eung Ju
authors.initials: EJ
authors.lastname: Kim
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Kim
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
mesh_terms: D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000187:drug effects / Q000378:metabolism*
chemical_list: C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol
keywords: ABC transporters; HDL; adipocytes; apolipoprotein AI; cholesterol