肝アセチルCoAは脂肪組織の炎症と肝臓のインスリン抵抗性および2型糖尿病を関連付けています
Rachel J Perry1, João-Paulo G Camporez2, Romy Kursawe2
1Howard Hughes Medical Institute, Yale University, New Haven, CT 06519, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.
Cell
|February 10, 2015
まとめ
インスリンは通常,脂肪組織の脂解によって肝アセチルCoAを減少させ,肝臓のグルコース産生を抑制する. この経路は2型糖尿病で破壊され,炎症とインスリン抵抗性を結びつける.
科学分野:
- 代謝の調節 メタボリックの調節
- 糖尿病の分子メカニズム
- 肝臓のグルコース生産
背景:
- 肝臓のグルコース産生 (HGP) のインスリン抑制障害は,2型糖尿病 (T2D) の病原性にとって中心的なものです.
- この障害を誘発する正確な分子機構は,完全に理解されていません.
研究 の 目的:
- インスリンがHGP.を抑制する分子メカニズムの解明.
- 肥満,炎症,肝臓のインスリン抵抗性を結びつける重要な分子因子を特定する.
主な方法:
- 新しい in vivo メタボロミックスのアプローチ.
- 遺伝子組み換えマウス (インスリンシグナル消去,脂肪トリグリセリドリパース欠乏症) と高脂肪食マウスでの研究.
- IL-6の中和と輸注への介入.
主要な成果:
- インスリンは,抑制された白脂肪組織 (WAT) の脂解によって肝アセチルCoAを減少させ,ピルバ酸カルボキシラーゼ (PC) のフクロスを減少させ,HGPを抑制します.
- このメカニズムは,高脂肪食を摂取したラットでは障害があり,炎症 (IL-6) と関連しています.
- インスリンシグナル伝達と脂解の回復は,IL-6の中和によって観察されました.
結論:
- WAT由来の肝アセチルCoAは,インスリンによるHGP抑制の主な調節剤である.
- 炎症誘発性IL-6は,この経路を阻害することによって,肥満およびT2Dにおける肝臓インスリン抵抗性に貢献します.
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