title: Inhibition of inflammatory signaling pathways in 3T3-L1 adipocytes by apolipoprotein A-I.
abstract: Activation of inflammatory signaling pathways links obesity with metabolic disorders. TLR4-mediated activation of MAPKs and NF-κB are 2 such pathways implicated in obesity-induced inflammation. Apolipoprotein A-I (apoA-I) exerts anti-inflammatory effects on adipocytes by effluxing cholesterol from the cells via the ATP binding cassette transporter A1 (ABCA1). It is not known if these effects involve inhibition of inflammatory signaling pathways by apoA-I. This study asks if apoA-I inhibits activation of MAPKs and NF-κB in mouse 3T3-L1 adipocytes and whether this inhibition is ABCA1 dependent. Incubation of differentiated 3T3-L1 adipocytes with apoA-I decreased cell surface expression of TLR4 by 16 ± 2% and synthesis of the TLR4 adaptor protein, myeloid differentiation primary response 88, by 24 ± 4% in an ABCA1-dependent manner. ApoA-I also inhibited downstream activation of MAPKs, such as ERK, p38MAPK, and JNK, as well as expression of proinflammatory adipokines in bacterial LPS-stimulated 3T3-L1 adipocytes in an ABCA1-dependent manner. ApoA-I, by contrast, suppressed nuclear localization of the p65 subunit of NF-κB by 30 ± 3% in LPS-stimulated 3T3-L1 adipocytes in an ABCA1-independent manner. In conclusion, apoA-I inhibits TLR4-mediated inflammatory signaling pathways in adipocytes by preventing MAPK and NF-κB activation.-Sultana, A., Cochran, B. J., Tabet, F., Patel, M., Cuesta Torres, L., Barter, P. J., Rye, K.-A. Inhibition of inflammatory signaling pathways in 3T3-L1 adipocytes by apolipoprotein A-I.
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and.
authors.forename: Afroza
authors.initials: A
authors.lastname: Sultana
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and.
authors.forename: Blake J
authors.initials: BJ
authors.lastname: Cochran
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and.
authors.forename: Mili
authors.initials: M
authors.lastname: Patel
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and.
authors.forename: Luisa Cuesta
authors.initials: LC
authors.lastname: Torres
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, University of New South Wales Australia, Sydney, New South Wales, Australia; and Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia k.rye@unsw.edu.au karye@ozemail.com.au.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D018932:Chemokine CCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C577833:Abca1 protein, mouse; C491768:Ccl2 protein, mouse; C507780:Myd88 protein, mouse; C498144:Rela protein, mouse; C493487:Tlr4 protein, mouse
keywords: ABCA1; MAPK; NF‐κB