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二甲双胍通过抑制肝脏载脂蛋白A5表达降低ob/ob肥胖小鼠的血浆甘油三酯水平

[Metformin reduces plasma triglycerides in ob/ob obese mice via inhibiting the hepatic apoA5 expression].

作者信息

Huang Xiansheng, Li Rong, Chen Luzhu, Dai Wen

机构信息

Department of Cardiovascular Medicine, Second Xiangya Hospital, 
Central South University, Changsha 410011, China

Department of Stomatology, Second Xiangya Hospital, 
Central South University, Changsha 410011, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Dec 28;42(12):1389-1394. doi: 10.11817/j.issn.1672-7347.2017.12.006.

DOI:10.11817/j.issn.1672-7347.2017.12.006
PMID:29317579
Abstract

To investigate the role of apolipoprotein A5 (apoA5) in the pathogenesis of obesity-related hypertriglyceridemia and the related therapeutic effects of metformin.
 Methods: The ob/ob mice were treated with regular chow diet and metformin for 4 weeks, and the levels of hepatic triglyceride (TG) and apoA5 were measured. Hepatic IAR20 cells were treated with metformin and/or apoA5 siRNAs, and then cellular TG contents and apoA5 expression were determined.
 Results: High plasma and hepatic levels of apoA5 and TG were found in ob/ob mice. The plasma levels of apoA5 were positively correlated with plasma TG in these mice. Metformin could dose-dependently decrease the plasma and hepatic levels of apoA5 and TG in ob/ob mice. Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression, these effects were attenuated by knockdown of apoA5.
 Conclusion: Hepatic apoA5 is up-regulated in ob/ob mice, which contributes to the elevation of plasma TG. Metformin could inhibit hepatic apoA5 expression, leading to the reduction of the plasma level of TG.

摘要

探讨载脂蛋白A5(apoA5)在肥胖相关高甘油三酯血症发病机制中的作用以及二甲双胍的相关治疗效果。方法:对ob/ob小鼠给予常规饲料和二甲双胍治疗4周,检测肝脏甘油三酯(TG)水平和apoA5水平。用二甲双胍和/或apoA5小干扰RNA处理肝脏IAR20细胞,然后测定细胞内TG含量和apoA5表达。结果:在ob/ob小鼠中发现血浆和肝脏中apoA5及TG水平较高。这些小鼠血浆中apoA5水平与血浆TG呈正相关。二甲双胍可剂量依赖性降低ob/ob小鼠血浆和肝脏中apoA5及TG水平。二甲双胍还可剂量依赖性降低细胞内TG含量和apoA5表达,敲低apoA5可减弱这些作用。结论:ob/ob小鼠肝脏中apoA5上调,这导致血浆TG升高。二甲双胍可抑制肝脏apoA5表达,从而降低血浆TG水平。

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