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エンドウ ヤスヒロ
YASUHIRO ENDO
遠藤 康弘 所属 新潟薬科大学 医療技術学部 学部付 職種 准教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2024/10 |
| 形態種別 | 論文 - 研究論文（学術雑誌） |
| 標題 | Liver-specific Lxr inhibition represses reverse cholesterol transport in cholesterol-fed mice. |
| 執筆形態 | 単著（従来区分） |
| 掲載誌名 | Atherosclerosis |
| 掲載区分 | 国外 |
| 巻・号・頁 | 397,pp.117578-117578 |
| 著者・共著者 | Takafumi Nishida,Makoto Ayaori,Junko Arakawa,Yumiko Suenaga,Kazusa Shiotani,Harumi Uto-Kondo,Tomohiro Komatsu,Kazuhiro Nakaya,Yasuhiro Endo,Makoto Sasaki,Katsunori Ikewaki |
| 概要 | BACKGROUND AND AIMS: High density lipoprotein (HDL) exerts an anti-atherosclerotic effect via reverse cholesterol transport (RCT). Several phases of RCT are transcriptionally controlled by Liver X receptors (Lxrs). Although macrophage Lxrs reportedly promote RCT, it is still uncertain whether hepatic Lxrs affect RCT in vivo. METHODS: To inhibit Lxr-dependent pathways in mouse livers, we performed hepatic overexpression of sulfotransferase family cytosolic 2B member 1 (Sult2b1) using adenoviral vector (Ad-Sult2b1). Ad-Sult2b1 or the control virus was intravenously injected into wild type mice and Lxrα/β double knockout mice, under a normal or high-cholesterol diet. A macrophage RCT assay and an HDL kinetic study were performed. RESULTS: Hepatic Sult2b1 overexpression resulted in reduced expression of Lxr-target genes - ATP-binding cassette transporter G5/G8, cholesterol 7α hydroxylase and Lxrα itself - respectively reducing or increasing cholesterol levels in HDL and apolipoprotein B-containing lipoproteins (apoB-L). A macrophage RCT assay revealed that Sult2b1 overexpression inhibited fecal excretion of macrophage-derived 3H-cholesterol only under a high-cholesterol diet. In an HDL kinetic study, Ad-Sult2b1 promoted catabolism/hepatic uptake of HDL-derived cholesterol, thereby reducing fecal excretion. Finally, in Lxrα/β double knockout mice, hepatic Sult2b1 overexpression increased apoB-L levels, but there were no differences in HDL levels or RCT compared to the control, indicating that Sult2b1-mediated effects on HDL/RCT and apoB-L were distinct: the former was Lxr-dependent, but not the latter. CONCLUSIONS: Hepatic Lxr inhibition negatively regulates circulating HDL levels and RCT by reducing Lxr-target gene expression. |
| DOI | 10.1016/j.atherosclerosis.2024.117578 |
| PMID | 38797615 |