メラノコルチン依存によるmTOR活性化による肝臓ERホメオスタシス

Claus Brandt¹, Hendrik Nolte², Sinika Henschke¹

¹Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.

Cell

|November 17, 2018

まとめ

感覚的な食物知覚は神経経路を活性化することで栄養素の処理に肝臓を準備しますこの経路は視床下部と交感神経系を巻き込み肝臓を準備します

科学分野:

メタボリズム
神経内分泌学
細胞生物学

背景:

栄養素の摂取に肝臓の適応は代謝のホメオスタシスにとって極めて重要です
肝臓内プラズマ網膜 (ER) の機能は,タンパク質合成と脂質代謝に不可欠です.
感覚信号と代謝調節の相互作用は完全に理解されていません.

研究の目的:

早期の肝臓適応の開始における感覚的食物知覚の役割を調査する.
これらの吸収前代謝反応を媒介する神経経路を解明する.
肝臓が栄養素の流入を準備する際の重要な分子シグナルキャスケードを特定する.

主な方法:

視光遺伝学と化学遺伝学を使って視床下部のPOMCニューロンを in vivoで操作した.
肝臓のmTORシグナル伝達,Xボックス結合タンパク質1 (Xbp1) スプライシング,ERストレス遺伝子発現を測定した.
フォスファディチルコリン合成とER形態を評価した.
メラノコルチン経路と交感神経活動 (SNA) の役割を調査した.

主要な成果:

感覚的な食物知覚だけで,肝臓の mTOR シグナル伝達,Xbp1 スプライシング,ER-ストレス遺伝子誘導,およびフォスファディチルコリン合成を誘発した.
これらの早期の反応は肝臓ERの有意な形態的改造につながった.
下垂体POMCニューロンの活性化はこれらの肝臓反応を模倣し,MC4R欠乏はそれらを弱めた.
POMCニューロンの活性化により,肝臓へのSNAが強化され,ノレピネフリン投与は観察された肝臓の適応を複製した.

結論:

感覚的な食物知覚は食事前後の調整を肝臓で開始します
この適応は,新型のメラノコルチン-SNA-mTOR-Xbp1s軸によって,下垂体POMCニューロンから発現します.
この発見により肝臓が感覚信号に基づいて栄養素を処理する重要な神経機構が明らかになりました

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