核受容体Rev-erbαは,昼間の熱生成性可塑性を制御する
Zachary Gerhart-Hines1,2, Dan Feng1,2, Matthew J Emmett1,2
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Nature
|October 29, 2013
まとめ
核受容体Rev-erbα (Nr1d1) は,日々の体温リズムと寒さに適応する能力を結びつける. Rev-erbαの損失は冷たい耐性を向上させ,温度リズムを乱します.
科学分野:
- クロノバイオロジー クロノバイオロジー
- メタボリック・レギュレーション
- 哺乳類生理学について
背景:
- 哺乳類は,日々の体温リズムと,寒さに対するホメオスタティックな反応を示します.
- シルカディアンリズムと寒さへの適応の間の分子関連は不明である.
研究 の 目的:
- 昼間の体温リズムと熱生成の調整における核受容体Rev-erbα (Nr1d1) の役割を調査する.
- Rev-erbαが茶色脂肪組織 (BAT) の機能と寒さ耐性を影響するメカニズムを解明する.
主な方法:
- Rev-erbα 削除 (Rev-erbα-null) とワイルドタイプのコントロールを用いたマウスモデルを使用した.
- 日中の異なる時間帯 (Zeitgeber時間) で評価された寒さ耐性.
- 測定された解離タンパク質1 (Ucp1) の表現は,BATと体温リズムで測定された.
主要な成果:
- Rev-erbα発現は,寒さ耐性と逆相関する; 05:00 (ZT22) の低発現は, 17:00 (ZT10) の高発現よりも優れた耐性と相関する.
- Rev-erbα-nullマウスは,特に17時00分に,寒さに耐える能力が著しく向上した.
- Rev-erbαは,BATにおけるUcp1発現を直接抑制し,その欠如は,熱中性でもUcp1レベルが上昇する.
- Rev-erbαの遺伝的喪失は,正常な体温とBAT活動リズムを廃止する.
結論:
- Rev-erbαは,サーカディアンと熱生成経路の間の重要な分子リンクとして作用します.
- Rev-erbαは,BAT機能,Ucp1誘導,および毎日の体温リズムの主なレギュラーである.
- Rev-erbαの抑制機能は,熱生成を寒さに曝されるような環境的課題に適応させるのに不可欠です.
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