マクロファージの炎症性カテキオラミン分解は,老化時に脂質分解を鈍化させる
Christina D Camell1,2, Jil Sander3, Olga Spadaro1,2
1Department of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|September 28, 2017
まとめ
老化により,ノラドレナリンの可用性が低下し,脂肪の分解 (脂解) が妨げられます. マクロファージにおけるNLRP3炎症体とモノアミン酸化酵素A (MAOA) を標的にすることで,脂質分解が回復し,老化における代謝の健康上の利点がもたらされます.
科学分野:
- 免疫学
- メタボリズム
- 老化に関する研究
背景:
- カテコアミン誘発の脂質分解は エネルギー生成に不可欠で 年齢とともに減少します
- この年齢関連の減少は,内臓の肥満,運動能力の低下,体温調節障害と関連しています.
- 正常な脂肪細胞のシグナル伝達にもかかわらず,老化における脂質分解の障害の背後にある正確なメカニズムは不明である.
研究 の 目的:
- 脂肪組織のマクロファージが年齢に関係する脂質分解の減少における役割を調査する.
- 老化における脂肪の動員障害を媒介する分子経路を特定する.
- 年齢に関連した代謝機能障害の潜在的治療目標を探求する.
主な方法:
- 脂肪組織マクロファージの全トランスクリプトーム解析
- NLRP3炎症体の成分と特定の遺伝子 (GDF3,MAOA) の遺伝的削除
- 脂解,ノラドレナリン濃度,主要な脂解酵素 (ATGL,HSL) の測定
主要な成果:
- 加齢はNLRP3炎症体を通して脂肪のマクロファージにおけるカテコアミン分解遺伝子を上限化する.
- NLRP3の消去は,GDF3とMAOAをダウンレギュレーションすることによって,脂解を回復します.
- MAOAの抑制は,年齢に関連したノラドレナリン減少を逆転させ,脂解を回復させます.
結論:
- アディポス組織マクロファージは,カテキオラミンの分解を通して,年齢に関連する脂質分解の障害を調節する.
- 神経免疫代謝軸,特にNLRP3とMAOAをターゲットにすることで,脂質分解を回復できます.
- この研究は,年齢に関連した代謝低下と炎症を緩和するための新しい戦略を示唆しています.
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