脂肪組織内のストレスシグナル伝達経路は,肝臓のインスリン抵抗性を調節する
Guadalupe Sabio1, Madhumita Das, Alfonso Mora
1Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (New York, N.Y.)
|December 6, 2008
まとめ
高脂肪食はc-Jun NH2端末キナーゼ1 (JNK1) を活性化し,インスリン抵抗性を引き起こします. 脂肪組織におけるJNK1を標的にすることは,肝臓のインスリン抵抗性を予防することによって,代謝症候群を治療することができます.
科学分野:
- メタボリック疾患は,
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
背景:
- 高脂肪食はc-Jun NH2端末キナーゼ1 (JNK1) を活性化させ,インスリン抵抗性に関与する重要な調節因子である.
- インスリン抵抗性はメタボリックシンドロームの主要な特徴であり,心臓病,脳卒中,および2型糖尿病のリスクを増加させる状態の群である.
- 脂肪組織におけるJNK1シグナル伝達は,代謝障害の潜在的な治療標的である.
研究 の 目的:
- 食事によるインスリン抵抗性における脂肪組織JNK1の特定の役割を調査する.
- 脂肪系JNK1が肝臓のインスリン感受性に影響を与える分子機構を解明する.
主な方法:
- 脂肪組織における選択的なJNK1遺伝子除去による遺伝子工学によるマウスの生成.
- ダイエット誘発の代謝変化を評価するために,高脂肪食の投与.
- インスリン抵抗性マーカー,炎症性サイトカイン発現,肝臓と脂肪組織における主要なタンパク質シグナル伝達経路の分析.
主要な成果:
- 脂肪組織における選択的JNK1欠乏症は,高脂肪食によるインスリン抵抗性を肝臓で著しく抑制した.
- 脂肪組織におけるJNK1の活性化は,インタールイキン-6 (IL-6) の分泌を促進した.
- アディポス由来IL-6は,肝臓におけるシトカインシグナル伝達3抑制剤 (SOCS3) の発現を増加させ,肝臓におけるインスリン抵抗性のメディエーターとして知られています.
結論:
- 脂肪組織内のJNK1の活性化は,肝臓のインスリン抵抗性の重要な要因である.
- 脂肪組織におけるJNK1シグナル伝達をターゲットにすることは,代謝症候群とインスリン抵抗性との闘いにおける有望な治療戦略です.
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