title: High-density lipoprotein and apolipoprotein A-I inhibit palmitate-induced translocation of toll-like receptor 4 into lipid rafts and inflammatory cytokines in 3T3-L1 adipocytes.
abstract: Saturated fatty acids (SFAs) activate toll-like receptor 4 (TLR4) signal transduction in macrophages and are involved in the chronic inflammation accompanying obesity. High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) produce anti-inflammatory effects via reverse cholesterol transport. However, the underlying mechanisms by which HDL and apoA-I inhibit inflammatory responses in adipocytes remain to be determined. Here we examined whether palmitate increases the translocation of TLR4 into lipid rafts and whether HDL and apoA-I inhibit inflammation in adipocytes. Palmitate exposure (250 μM, 24 h) increased interleukin-6 and tumor necrosis factor-α gene expressions and translocation of TLR4 into lipid rafts in 3T3-L1 adipocytes. Pretreatment with HDL and apoA-I (50 μg/mL, 6 h) suppressed palmitate-induced inflammatory cytokine expression and TLR4 translocation into lipid rafts. Moreover, HDL and apoA-I inhibited palmitate-induced phosphorylation of nuclear factor-kappa B. HDL showed an anti-inflammatory effect via ATP-binding cassette transporter G1 and scavenger receptor class B, member 1, whereas apoA-I showed an effect via ATP-binding cassette transporter A1. These results demonstrated that HDL and apoA-I reduced palmitate-potentiated TLR4 trafficking into lipid rafts and its related inflammation in adipocytes via these specific transporters.
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan.
authors.forename: Hodaka
authors.initials: H
authors.lastname: Yamada
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan. Electronic address: to-ume@omiya.jichi.ac.jp.
authors.forename: Tomio
authors.initials: T
authors.lastname: Umemoto
authors.affiliation: Internal Medicine, Hitachi Omiya Saiseikai Hospital, 3033-3 Tagochicho, Hitachiomiya, Ibaraki 319-2256, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Internal Medicine, Nerima Hikarigaoka Hospital, 2-11-1 Hikarigaoka, Nerima, Tokyo 179-0072, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kawakami
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kakei
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Momomura
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan; Division of Endocrinology and Metabolism, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara 329-2763, Tochigi, Japan.
authors.forename: San-E
authors.initials: SE
authors.lastname: Ishikawa
authors.affiliation: First Department of Comprehensive Medicine, Jichi Medical University Saitama Medical Center, Amanuma, 1-847 Amanumacho, Omiya, Saitama 330-8503, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D016632:Apolipoprotein A-I / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D010168:Palmitates / Q000494:pharmacology*; D021381:Protein Transport; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D016207:Cytokines; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D010168:Palmitates; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: Adipocytes; Apolipoprotein A-I; High-density lipoprotein; Lipid raft; Toll-like receptor 4