文献类型： 外文期刊

作者： Shen, Weili ² ; Hao, Jiejie ⁴ ; Feng, Zhihui ⁵ ; Tian, Chuan ⁵ ; Chen, Weijun ⁷ ; Packer, Lester ⁸ ; Shi, Xianglin ⁹ ; Za ¹ ;

作者机构： 1.Xi An Jiao Tong Univ, Inst Mitochondrial Biol & Med, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China

2.Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai Key Lab Vasc Biol,Ruijin Hosp, Shanghai 200030, Peoples R China

3.Shanghai Jiao Tong Univ, Sch Med, Dept Hypertens, Ruijin Hosp, Shanghai 200030, Peoples R China

4.Ocean Univ China, Sch Med & Pharm, Qingdao, Peoples R China

5.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China

6.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China

7.Chinese Acad Trop Agr Sci, Coconut Res Inst, Wenchang, Hainan, Peoples R China

8.Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA USA

9.Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY USA

10.Xi An Jiao Tong Univ, Coll Med, Dept Pharmacol, Xian 710049, Peoples R China

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.