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アデノシンは,茶色の脂肪組織を活性化し,A2A受容体を通してベージュの脂肪細胞を勧誘する
Thorsten Gnad1, Saskia Scheibler2, Ivar von Kügelgen1
1Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany.
Nature
|October 16, 2014
まとめ
アデノシンは,A2A受容体を通して茶色脂肪組織 (BAT) を活性化させ,エネルギー消費を増加させます. この発見は,肥満と代謝障害に対する新しい治療戦略を提供します.
科学分野:
- 代謝と内分泌学について
- 細胞生物学 細胞生物学
- 肥満に関する研究
背景:
- 茶色脂肪組織 (BAT) は,エネルギー消費に不可欠であり,抗肥満治療の標的である.
- 現在のBAT活性化戦略 (冷たいベータアドレナゲンアゴニスト) には臨床的な限界があります.
- 人間のBAT機能におけるアデノシンシグナル伝達の役割は,ほとんど知られていなかった.
研究 の 目的:
- アデノシンとその受容体の役割について,ヒトとネズミの茶色脂肪組織で調査する.
- 肥満の潜在的な治療目標としてアデノシンシグナル伝達を調査する.
主な方法:
- アデノシンがヒトとマウインのブラウンアディポサイトに及ぼす効果を in vitro で研究した.
- 交感神経刺激中のアデノシン放出量.
- ネズミの遺伝子および薬理学的アプローチを使用して,BATにおけるアデノシン受容体の発現と機能を分析した.
- A2A受容体調節が発熱,エネルギー消費,食事による肥満に与える影響を評価した.
主要な成果:
- アデノシンは,ナノモラー濃度でヒトおよびマウリンの茶色脂肪細胞を活性化します.
- アデノシンは,交感神経刺激中にBATから放出されます.
- アデノシンA2A受容体は,BATにおいて高度に表現され,アデノシンの効果を媒介する.
- A2A受容体の活性化により,BAT熱生成,エネルギー消費が増加し,ベージュ色の脂肪細胞の形成が誘発されます.
- マウスにおけるA2Aアゴニスト治療は,高脂肪食条件下で肥満を軽減し,グルコース耐性を改善しました.
結論:
- アデノシン-A2A受容体のシグナリングは,BATの交感活性化において重要な生理学的役割を果たします.
- アデノシンA2A受容体をターゲットにすることは,抗肥満療法を開発するための有望な新しい戦略です.
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