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Assessing Whole-Body Lipid-Handling Capacity in Mice
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昼間の血清脂質は肝臓の脂質生成と周辺脂肪酸の使用を統合する
Sihao Liu1, Jonathan D Brown, Kristopher J Stanya
11] Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA [2].
Nature
|October 25, 2013
まとめ
研究者らは,肝臓のPPARδが特定の脂質,PC ((18:0/18:1) を介して筋肉の脂肪使用を制御する新しい経路を発見しました. この発見は,肝臓の脂質生成を筋肉のエネルギー使用と結びつけ,肥満のような代謝障害に影響を与える可能性がある.
科学分野:
- メタボリック調節 メタボリック調節
- シルカディアンリズムは,
- 脂質代謝 脂質代謝とは
背景:
- 肝臓の新たなリポゲネシスは,日中リズムに従って,グルコースを脂肪に変換し,Rev-erbα/β.のような要因によって調節されます.
- 肝臓のリポゲネシスの障害は,全身の代謝問題と関連しており,臓器間のコミュニケーションを示唆しています.
研究 の 目的:
- ダークサイクル中のリズム性脂質合成の転写活性化剤を特定する.
- エネルギーホメオスタシスのために周辺組織と通信する肝臓の役割を明らかにする.
- 肝臓の脂質生成と筋肉脂肪の利用を結びつけるPPARδ依存の経路を定義する.
主な方法:
- 肝臓における昼間のリポゲン遺伝子発現におけるPPARδの役割を調査した.
- マウスの肝臓特異的なPPARδ活性化および肝細胞-Ppard消去モデルを使用した.
- 主要な循環する脂質を特定するために,偏りのない代謝産物プロフィールを採用した.
- 食事による肥満とdb/dbのマウスモデルでPCを18:0/18:1) 投与した.
主要な成果:
- PPARδは,食事中に肝臓のリポゲン遺伝子の昼間発現を制御する.
- 肝臓のPPARδの活性化により,筋肉の脂肪酸の吸収が強化され,そのデリレーションにより脂肪酸の吸収が減少する.
- フォスファディチルコリン18:0/18:1 (PC(18:0/18:1)) を,昼間の肝臓PPARδによって調節される血清脂質として特定した.
- PC(18:0/18:1) は,食後の脂質を低下させ,PPARα経由で筋肉脂肪酸の使用を増加させます.
- 高脂肪食はリズムPCの産生を妨害する;投与はdb/dbのマウスのメタボリックホメオスタシスを改善する.
結論:
- 肝臓にあるPPARδ-PC(18:0/18:1) シグナリング軸は,筋肉脂質の利用を調節する.
- この経路は,肝臓の脂質合成と周辺のエネルギー消費を統合します.
- この昼間のシグナリングの調節障害は,肥満のような代謝障害に寄与する可能性があります.
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