Lipoamide or lipoic acid stimulates mitochondrial biogenesis in 3T3-L1 adipocytes via the endothelial NO synthase-cGMP-protein kinase G signalling pathway
文献类型: 外文期刊
第一作者: Liu, Jiankang
作者: Liu, Jiankang;Shen, Weili;Shen, Weili;Hao, Jiejie;Feng, Zhihui;Tian, Chuan;Feng, Zhihui;Tian, Chuan;Chen, Weijun;Packer, Lester;Shi, Xianglin;Zang, Weijin
作者机构:
关键词: lipoic acid;lipoamide;mitochondria;peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha);mitochondrial transcription factor A (TFAM);nuclear respiratory factor 1 (NRF1)
期刊名称:BRITISH JOURNAL OF PHARMACOLOGY ( 影响因子:8.739; 五年影响因子:7.954 )
ISSN: 0007-1188
年卷期: 2011 年 162 卷 5 期
页码:
收录情况: SCI
摘要: BACKGROUND AND PURPOSE Metabolic dysfunction due to loss of mitochondria plays an important role in diabetes, and stimulation of mitochondrial biogenesis by anti-diabetic drugs improves mitochondrial function. In a search for potent stimulators of mitochondrial biogenesis, we examined the effects and mechanisms of lipoamide and alpha-lipoic acid (LA) in adipocytes. EXPERIMENTAL APPROACH Differentiated 3T3-L1 adipocytes were treated with lipoamide or LA. Mitochondrial biogenesis and possible signalling pathways were examined. KEY RESULTS Exposure of 3T3-L1 cells to lipoamide or LA for 24 h increased the number and mitochondrial mass per cell. Such treatment also increased mitochondrial DNA copy number, protein levels and expression of transcription factors involved in mitochondrial biogenesis, including PGC-1 alpha, mitochondrial transcription factor A and nuclear respiratory factor 1. Lipoamide produced these effects at concentrations of 1 and 10 mu mol center dot L-1, whereas LA was most effective at 100 mu mol center dot L-1. At 10 mu mol center dot L-1, lipoamide, but not LA, stimulated mRNA expressions of PPAR-gamma, PPAR-alpha and CPT-1 alpha. The potency of lipoamide was 10-100-fold greater than that of LA. Lipoamide dose-dependently stimulated expression of endothelial nitric oxide synthase (eNOS) and formation of cGMP. Knockdown of eNOS (with small interfering RNA) prevented lipoamide-induced mitochondrial biogenesis, which was also blocked by the soluble guanylate cyclase inhibitor, ODQ and the protein kinase G (PKG) inhibitor, KT5823. Thus, stimulation of mitochondrial biogenesis by lipoamide involved signalling via the eNOS-cGMP-PKG pathway. CONCLUSIONS AND IMPLICATIONS Our data suggest that lipoamide is a potent stimulator of mitochondrial biogenesis in adipocyte, and may have potential therapeutic application in obesity and diabetes.
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