乙酰丙酮氧钒化合物诱导的活性氧生成在3T3L1脂肪细胞脂解和糖代谢过程中的调节作用

doi:10.5246/jcps.2015.11.093

中国药学(英文版) ›› 2015, Vol. 24 ›› Issue (11): 726-733.DOI: 10.5246/jcps.2015.11.093

乙酰丙酮氧钒化合物诱导的活性氧生成在3T3L1脂肪细胞脂解和糖代谢过程中的调节作用

李逸, 刘竟成, 于游, 卞卫霞, 胡霞, 杨晓改^*

北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2015-06-01 修回日期:2015-07-30 出版日期:2015-11-20 发布日期:2015-08-15
通讯作者: Tel.: 86-10-82805956, E-mail: yxg@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 20871008 and 21171011).

Role of vanadyl acetylacetonate-induced elevation of reactive oxygen species in the regulation of lipolysis and glucose metabolism in 3T3L1 adipocytes

Yi Li, Jingcheng Liu, You Yu, Weixia Bian, Xia Hu, Xiaogai Yang^*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2015-06-01 Revised:2015-07-30 Online:2015-11-20 Published:2015-08-15
Contact: Tel.: 86-10-82805956, E-mail: yxg@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 20871008 and 21171011).

摘要/Abstract

摘要：

本研究以分化的3T3L1 脂肪细胞为模型, 研究了具有抗糖尿病活性的钒化合物VO(acac)₂引起的活性氧物种水平升高在3T3L1脂肪细胞脂解和糖代谢过程中的调节作用。共聚焦荧光显微镜的结果显示, 在高糖刺激的3T3L1脂肪细胞中,VO(acac)₂可引起细胞的ROS水平升高; 利用NADPH氧化酶的两种特异性抑制剂可降低此化合物诱导产生的活性氧水平。同时, 蛋白免疫印迹的结果显示, ROS水平的下降也可相应降低钒化合物引起的AKT的活性以及脂代谢信号路径中的关键调控蛋白HSL以及perilipin的磷酸化水平; 也可引起葡萄糖转运调控相关的AS160和糖原合成有关的GSK3β的磷酸化水平的相应下降。这说明, 钒化合物引起的ROS水平的升高应可能作为一个代谢信号通过激活AKT信号通路而不是通过其直接作用，从而抑制脂解、促进葡萄糖转运和糖原合成。本研究将为钒化合物的进一步开发和应用提供理论依据。

关键词: 乙酰丙酮氧钒化合物, 脂解, 活性氧物种, 糖代谢, 3T3L1细胞

Abstract:

In the present study, we investigated the role of reactive oxygen species (ROS) elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate (VO(acac)₂), in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO(acac)₂ induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis (HSL and perilipin) were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.

Key words: Vanadyl acetylacetonate, Lipolysis, Reactive oxygen species, Glucose metabolism, 3T3L1 adipocytes

中图分类号:

R916.3

Supporting:

李逸, 刘竟成, 于游, 卞卫霞, 胡霞, 杨晓改. 乙酰丙酮氧钒化合物诱导的活性氧生成在3T3L1脂肪细胞脂解和糖代谢过程中的调节作用[J]. 中国药学(英文版), 2015, 24(11): 726-733.

Yi Li, Jingcheng Liu, You Yu, Weixia Bian, Xia Hu, Xiaogai Yang. Role of vanadyl acetylacetonate-induced elevation of reactive oxygen species in the regulation of lipolysis and glucose metabolism in 3T3L1 adipocytes[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(11): 726-733.

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乙酰丙酮氧钒化合物诱导的活性氧生成在3T3L1脂肪细胞脂解和糖代谢过程中的调节作用

Role of vanadyl acetylacetonate-induced elevation of reactive oxygen species in the regulation of lipolysis and glucose metabolism in 3T3L1 adipocytes

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