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α-硫辛酸和乙酰左旋肉碱补充性的促进小鼠3T3-L1脂肪细胞线粒体生物合成 |
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R-α-Lipoic acid and acetyl-L-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes |
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Shen W., Liu K., Tian C., Yang L., Li X., Ren J., Packer L., Cotman C.W., Liu J. 2009/5/29 18:38:57 |
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Diabetologia, 2008, Volume 51, Issue 1
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Aims/hypothesis: The aim of the study was to address the importance of mitochondrial function in insulin resistance and type 2 diabetes, and also to identify effective agents for ameliorating insulin resistance in type 2 diabetes. We examined the effect of two mitochondrial nutrients, R-α-lipoic acid (LA) and acetyl-l-carnitine (ALC), as well as their combined effect, on mitochondrial biogenesis in 3T3-L1 adipocytes. Methods: Mitochondrial mass and oxygen consumption were determined in 3T3-L1 adipocytes cultured in the presence of LA and/or ALC for 24 h. Mitochondrial DNA and mRNA from peroxisome proliferator-activated receptor gamma and alpha (Pparg and Ppara) and carnitine palmitoyl transferase 1a (Cpt1a), as well as several transcription factors involved in mitochondrial biogenesis, were evaluated by real-time PCR or electrophoretic mobility shift (EMSA) assay. Mitochondrial complexes proteins were measured by western blot and fatty acid oxidation was measured by quantifying CO2 production from [1-14C] palmitate. Results: Treatments with the combination of LA and ALC at concentrations of 0.1, 1 and 10 μmol/l for 24 h significantly increased mitochondrial mass, expression of mitochondrial DNA, mitochondrial complexes, oxygen consumption and fatty acid oxidation in 3T3L1 adipocytes. These changes were accompanied by an increase in expression of Pparg, Ppara and Cpt1a mRNA, as well as increased expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (Ppargc1a), mitochondrial transcription factor A (Tfam) and nuclear respiratory factors 1 and 2 (Nrf1 and Nrf2). However, the treatments with LA or ALC alone at the same concentrations showed little effect on mitochondrial function and biogenesis. Conclusions/interpretation: We conclude that the combination of LA and ALC may act as PPARG/A dual ligands to complementarily promote mitochondrial synthesis and adipocyte metabolism. © 2007 Springer-Verlag. |
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Correspondence Address: Liu, J.; Institute for Brain Aging and Dementia, University of California, 1261 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, United States; email: j.liu@uci.edu |
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疾病资源中心
摘自:《西氏内科学》,第23版
患者女性,21岁,因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解,但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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