GDF15に対する脳幹受容体による非恒常的体重調節

Jer-Yuan Hsu¹, Suzanne Crawley¹, Michael Chen¹

¹NGM Biopharmaceuticals, South San Francisco, California 94080, USA.

Nature

|September 28, 2017

まとめ

研究者はGDF15タンパク質の新しい受容体GFRALを特定しストレス中に体重と食物の摂取を制御していますこの発見はストレスが代謝にどのように影響し重量障害の治療対象となるかを説明します

科学分野:

神経科学
メタボリズム
分子生物学

背景:

ホメオスタティック状態は安定した体重を保つために下垂体回路に依存します
ストレスや病気状態は代謝適応のための代替神経経路を活性化します
これらの非ホメオスタティック経路の分子信号と受容体は以前は知られていなかった.

研究の目的:

GDF15の脳幹受容体を特定する栄養とエネルギー消費の重要な調節器
ストレス誘発の代謝反応に関与する神経回路の解明
アノレキシアと体重減少におけるGDF15-GFRAL信号伝達の役割を理解する.

主な方法:

GDF15の受容体としてGFRALの識別
ストレス下でのGfralノックアウトマウスの分析
マウスの脳幹と下流経路におけるGDF15-GFRALニューロン活性化の調査.

主要な成果:

GFRALはGDF15に対する脳幹受容体である.
Gfral ノックアウトマウスはストレス下では過食し,化学療法による体重減少に抵抗します.
GDF15は,ポステラ領域と核経路ソリタリウスのGFRAL発現ニューロンを活性化し,ストレス反応回路を開始します.

結論:

GDF15-GFRALシグナリングは,外周ストレスシグナルと栄養と体重の非恒常調節の間のメカニズム的リンクを提供します.
この経路はストレスや病気の時に代謝の課題に適応するのに極めて重要です
この発見は,エネルギー需要の変化を特徴とする疾患の治療のための潜在的な治療目標を提供します.

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