Assessment of the Retrograde Potential of Combined Silybin - Metformin for Alleviating Renal Tubular Lipotoxicity Associated with Electron Transport Dysfunction Induced by Methylglyoxal via Chrebp/Srebp1 and Further Modulation of Pgc1/Sirt3

Project: A - Government Institution › b - National Science and Technology Council

Project Details

Description

先前發現甲基乙二醛增加腎細胞脂質沉積,同時上調脂質生成蛋白,與糖尿性腎脂質堆積造成腎絲球硬化及腎小管間質傷害有關。高血糖也可透過ChREBP直接合成脂肪,對腎臟改變脂質代謝導致腎脂毒性。PGC-1α負責調控粒線體生成,氧氣代謝與能量恆定,SIRT3為下游標的,可直接調控粒腺體電子傳遞鏈或中間代謝產物及脂肪酸利用。已知SIRT3缺少會導致糖尿病腎纖維化,然迄今尚無甲基乙二醛與SIRT3相互作用之探討。水飛薊素與Metformin皆可活化SIRT3,但先前實驗中Metformin僅可保護甲基乙二醛引起的腎細胞凋亡,水飛薊素則能調節脂質代謝,兩者合併或可調控粒腺體,應可消弭腎臟脂質累積。
StatusFinished
Effective start/end date8/1/21 → 7/31/22

Keywords

  • Methylglyoxal stress
  • Renal lipotoxicity
  • Carbohydrate-responsive element-binding protein (ChREBP)
  • Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α)
  • NAD+-dependent deacetylase sirtuin-3 (SIRT3)
  • Silybin

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