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Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice 期刊论文

编号：

3046fc02-efd4-423f-b4cf-664f2a64bf33
作者：

Zhang, Jingjing#^[1,2,3,4]Cheng, Yanli(程艳丽)^[4,5]Gu, Junlian^[4];Wang, Shudong(王树东)^[4,5]Zhou, Shanshan(周珊珊)^[4,5]Wang, Yuehui(王越晖)^[5]Tan, Yi^[3,4,6,7];Feng, Wenke^[6,7];Fu, Yaowen(傅耀文)^[5]Mellen, Nicholas^[4];Cheng, Rui^[8];Ma, Jianxing^[8];Zhang, Chi(张驰)*^[3]Li, Zhanquan(李占全)*^[1,2]Cai, Lu(蔡露)*^[3,4,6,7]
语种：

英文
期刊：

CLINICAL SCIENCE ISSN：0143-5221 2016 年 130 卷 8 期 (625 - 641) ; APR 1
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关键词：

autophagy diabetic cardiomyopathy FGF21-knockout PPARa agonist (fibrate) Sirt1
摘要：

Fenofibrate (FF), as a peroxisome-proliferator-activated receptor alpha (PPAR alpha) agonist, has been used clinically for decades to lower lipid levels. In the present study, we examined whether FF can be repurposed to prevent the pathogenesi of the heart in Type 1 diabetes and to describe the underlying mechanism of its action. Streptozotocin (STZ)-induced diabetic mice and their age-matched control mice were treated with vehicle or FF by gavage every other day for 3 or 6 months. FF prevented diabetes-induced cardiac dysfunction (e.g. decreased ejection fraction and hypertrophy), inflammation and remodelling. FF also increased cardiac expression of fibroblast growth factor 21 (FGF21) and sirtuin 1 (Sirt1) in non-diabetic and diabetic conditions. Deletion of FGF21 gene (FGF21-KO) worsened diabetes-induced pathogenic effects in the heart. FF treatment prevented heart deterioration in the wild-type diabetic mice, but could not do so in the FGF21-KO diabetic mice although the systemic lipid profile was lowered in both wild-type and FGF21-KO diabetic mice. Mechanistically, FF treatment prevented diabetes-impaired autophagy, reflected by increased microtubule-associated protein 1A/1B-light chain 3, in the wild-type diabetic mice but not in the FGF21-KO diabetic mice. Studies with H9C2 cells in vitro demonstrated that exposure to high glucose (HG) significantly increased inflammatory response, oxidative stress and pro-fibrotic response and also significantly inhibited autophagy. These effects of HG were prevented by FF treatment. Inhibition of either autophagy by 3-methyladenine (3MA) or Sirt1 by sirtinol (SI) abolished FF's prevention of HG-induced effects. These results suggested that FF could prevent Type 1 diabetes-induced pathological and functional abnormalities of the heart by increasing FGF21 that may up-regulate Sirt1-mediated autophagy.
推荐引用方式
GB/T 7714：

Zhang Jingjing,Cheng Yanli,Gu Junlian, et al. Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice [J].CLINICAL SCIENCE,2016,130(8):625-641.
APA：

Zhang Jingjing,Cheng Yanli,Gu Junlian,Wang Shudong,&Cai Lu.(2016).Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice .CLINICAL SCIENCE,130(8):625-641.
MLA：

Zhang Jingjing, et al. "Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice" .CLINICAL SCIENCE 130,8(2016):625-641.
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