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継続的走運動および筋p62/Sqstm1は非アルコール性脂肪性肝炎の発症と進展を抑制する

三浦, 征 筑波大学 DOI:10.15068/0002008204

2023.09.04

概要

非アルコール性脂肪性肝炎 (Non-alcoholic steatohepatitis: NASH) は,肝硬変・
肝癌へと進行する重篤な肝疾患であり,予防・治療法の確立は重要な医療課題で
ある.NASH の発症と進展には,腸内細菌叢の菌体成分である lipopolysaccharide
(LPS) の肝への過剰流入とその貪食の遅延による炎症の蔓延が重要な役割を演
じるが,継続的な運動は,肝の組織マクロファージである Kupffer 細胞 (KCs) に
おける異物貪食能を向上させ,生体の LPS クリアランスを増大させることが明
らかになっている.これより,運動が KCs の異物貪食能の向上を介して LPS が
誘導する肝の炎症を減弱し,NASH の発症と進展を抑制する可能性が示唆され
ている.
NASH の発症と進展には肝外の複数臓器の異常が関与する.骨格筋は全身の
代謝制御を担っており,サルコペニア(骨格筋の萎縮と筋力低下)や骨格筋異常
によって生じるインスリン抵抗性は,筋-肝連関を介して NASH 発症と進展を促
進する.また,骨格筋は運動の中心器官であり,NASH の防御に対する運動の有
用性を考慮すると,NASH における骨格筋の役割を検証することは,NASH の病
態解明や予防・治療法の構築に重要であると考えられる.
p62 遺伝子欠失 (p62-KO) マウスは,中枢性の leptin 抵抗性に起因する過食肥
満を基盤に,高血圧,耐糖能異常,単純性脂肪肝などのヒトメタボリックシンド
ロームに即した表現型を示す.さらに,高脂肪食の摂 ...

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(参考文献)

和田聖大.(2020).継続的走運動は高脂肪食摂

p62 欠損マウスにおける肝の

炎症および線維化を抑制する.修士論文.

68

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