Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages

doi:10.1097/CM9.0000000000000333

科研成果详情

题名	Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages
作者	He, Xuan 1; Wang, Lei 1; Chen, Xiu-Fang2; Liang, Qiao 1; Wang, Wen-Qing 1; Lin, An-Qi 1; Yi, Long 1; Wang, Yong 1; Gao, Qian 1
发表日期	2019-07-20
发表期刊	CHINESE MEDICAL JOURNAL 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Atherosclerosis Macrophages Oxidized low-density lipoprotein Mitochondria Metabolism
其他关键词	OXIDATIVE STRESS ; INTERFERON-GAMMA ; ATHEROSCLEROSIS ; POLARIZATION ; INHIBITION ; SUPPRESSES ; EXPRESSION ; METAANALYSIS ; METABOLISM ; FISSION
摘要	Background: Macrophage accumulation in the vascular wall is a hallmark of atherosclerosis. Studies showed that shifting of oxidized lipids-induced inflammatory macrophages towards an anti-inflammatory phenotype by promoting oxidative metabolism attenuated atherosclerosis progression. Therefore, this study aimed to investigate whether metformin, which has ameliorated atherosclerosis in animal models and clinical trials, modulated oxidized low-density lipoprotein (Ox-LDL) induced inflammatory status in macrophages by regulating cellular oxidative metabolism. Methods: Murine raw264.7 macrophages were incubated with Ox-LDL (50 mu g/mL) in the presence or absence of metformin (15 mu mol/L) for 24 h. Real-time polymerase chain reaction was used to quantify the transcription of classically activated (M1) pro-inflammatory and alternatively activated (M2) anti-inflammatory markers and mitochondrial DNA copy numbers. Cellular reactive oxygen species (ROS) production and mitochondrial membrane potential were detected by immunofluorescence. Cellular adenosine triphosphate (ATP) synthesis, glucose uptake, and lactic acid production were measured by commercial kit and normalized to cellular lysates. Western blotting analysis was performed to detect the expression of mitochondrial fusion/fission related proteins, enzymes mediating lipid metabolism and signaling pathway of glucose transport. Differences between groups were analyzed using one-way analysis of variance. Results: Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 +/- 0.04 vs. 0.94 +/- 0.01, P = 0.003) and Resistin-like molecule alpha (0.67 +/- 0.08 vs. 1.78 +/- 0.34, P = 0.030). Conversely, Ox-LDL-diminished phosphorylation of Akt was up-regulated by metformin treatment (0.47 +/- 0.05 vs. 1.02 +/- 0.08, P = 0.040), associated with an improvement of mitochondrial function, characterized by decreased ROS generation (2.50 +/- 0.07 vs. 2.15 +/- 0.04, P = 0.040), increased lipid oxidation, and elevated cellular ATP production (0.026 +/- 0.001 vs. 0.035 +/- 0.003, P = 0.020). Moreover, merformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 +/- 0.04 vs. 1.03 +/- 0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 +/- 0.04 vs. 5.47 +/- 0.01, P < 0.001). Conclusion: This study suggested that targeting macrophage metabolism with new or existing drugs had therapeutic potential for the prevention and treatment of diabetes-accelerated atherosclerosis.
出版者	LIPPINCOTT WILLIAMS & WILKINS
出版地	PHILADELPHIA
ISSN	0366-6999
EISSN	2542-5641
卷号	132 期号:14 页码:1713-1722
DOI	10.1097/CM9.0000000000000333
页数	10
WOS类目	Medicine, General & Internal
WOS研究方向	General & Internal Medicine
WOS记录号	WOS:000480705500011
收录类别	SCIE ; PUBMED ; SCOPUS ; CSCD
学科领域	医药、卫生
URL	查看原文
CSCD记录号	CSCD:6540713
Pubmed记录号	31268904
PMC记录号	PMC6759109
Scopus记录号	2-s2.0-85070118286
通讯作者地址	[Gao, Qian]Medical School of Nanjing University,Science and Technology Bldg 217,No.22 Hankou Road,Nanjing, Jiangsu,210093,China
scopus学科分类	Medicine (all)
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17297
专题	检验医学院（生命科学学院、生物学实验教学中心）_生物化学与分子生物学系基础医学院（机能实验教学中心）
通讯作者	Gao, Qian
作者单位	1.Medical School of Nanjing University,Nanjing, Jiangsu,210093,China; 2.Department of Biochemistry,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,325035,China
推荐引用方式 GB/T 7714	He, Xuan,Wang, Lei,Chen, Xiu-Fang,et al. Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages[J]. CHINESE MEDICAL JOURNAL,2019,132(14):1713-1722.
APA	He, Xuan., Wang, Lei., Chen, Xiu-Fang., Liang, Qiao., Wang, Wen-Qing., ... & Gao, Qian. (2019). Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages. CHINESE MEDICAL JOURNAL, 132(14), 1713-1722.
MLA	He, Xuan,et al."Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages".CHINESE MEDICAL JOURNAL 132.14(2019):1713-1722.