PGC-1βによるSREBPの同活性化によって媒介される食中飽和脂肪の超脂血性効果
Jiandie Lin1, Ruojing Yang, Paul T Tarr
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|February 1, 2005
まとめ
高脂肪食は肝臓のPGC-1βとSREBPの発現を増加させ,高脂血症を促進する. PGC-1βは肝臓の脂肪を減らすが,血脂を増加させ,アテロゲネシスに寄与する.
科学分野:
- 代謝と分子生物学について
- 心血管科学の研究について
背景:
- PGC-1共活性化剤は,転写因子と核受容体を調節する.
- ステロール反応性元素結合タンパク質 (SREBPs) は,肝臓内のリポゲン遺伝子を制御する.
研究 の 目的:
- 高脂肪食による高脂血症およびアテロゲネシスにおけるPGC-1βの役割を調査する.
- PGC-1βが肝臓の脂質代謝と脂質タンパク質輸送に影響を与えるメカニズムを解明する.
主な方法:
- 高脂肪食を摂取した後の肝臓における遺伝子発現 (PGC-1β,SREBP1c,SREBP1a) の分析.
- PGC-1βのSREBPの同活性化とそのリポゲン遺伝子発現における役割の評価.
- 肝臓脂肪の蓄積と循環中の脂質レベルに対するPGC-1βの効果の評価.
- 肝臓X受容体アルファ (LXRalpha) とのPGC-1βの相互作用の調査.
主要な成果:
- 高脂肪食は,肝臓におけるPGC-1βとSREBP1c/1aを調節した.
- PGC-1βはSREBPを同活性化し,リポゲン遺伝子の発現を刺激し,SREBP媒介の効果には不可欠でした.
- PGC-1βは肝臓脂肪の蓄積を減らし,循環中のトリグリセリドとVLDLコレステロールを増加させた.
- PGC-1βはLXRalphaを同活性化し,脂質タンパク質の輸送を強化した.
結論:
- PGC-1βは,肝臓の脂質代謝において二重の役割を果たし,肝臓の脂肪を減少させながら,高脂血症を促進します.
- 食中の飽和脂肪酸は,PGC-1βおよびSREBPの活性化によって,高脂血症およびアテロゲネシスを誘発する可能性があります.
- PGC-1betaによるLXRalphaの同活性化は,リポプロテインの代謝の変化に寄与する.
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