α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects
α-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects
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DOI：
10.1016/j.bbalip.2014.12.013
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发表时间：
2015-03-01
影响因子：
4.8
通讯作者：
Moreno-Aliaga, Maria J.
中科院分区：
文献类型：
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作者：
Fernandez-Galilea, Marta;Perez-Matute, Patricia;Moreno-Aliaga, Maria J.
α-硫辛酸（α-Lip）是一种天然抗氧化剂，具有有益的抗肥胖特性。本研究的目的是研究 α-Lip 对超重/肥胖受试者皮下脂肪细胞线粒体生物发生和棕色样特征获得的假定影响。因此，将完全分化的人皮下脂肪细胞用α-Lip（100和250μM）处理24小时，以研究线粒体含量和形态、线粒体DNA（mtDNA）拷贝数、脂肪酸氧化酶和棕色/米色特征基因。还评估了 Sirtuin1/过氧化物酶体增殖物激活受体 γ、共激活剂 1 α (SIRT1/PGC-1 α) 通路的参与情况。我们的结果表明，通过电子显微镜和 mitotracker 绿色标记显示，α-Lip 增加了培养的人类脂肪细胞中的线粒体含量。此外，还观察到线粒体DNA含量的增加。这种增加伴随着 SIRT1 蛋白水平的上调、PGC-1 α 乙酰化的减少以及核呼吸因子 1 (Nrf1) 和线粒体转录因子 (Tfam) 的上调。还观察到耗氧量和脂肪酸氧化酶、肉碱棕榈酰转移酶 1 和酰基辅酶 A 氧化酶（CPT-1 和 ACOX）的增加。 α-Lip 处理的脂肪细胞表现出一些棕色线粒体的形态特征，并且 alpha-Lip 还诱导一些棕色/米色脂肪细胞标记物的上调，例如诱导细胞死亡的 DFFA 样效应子 a (Cidea) 和 T-box 1 (Tbx1)。此外，α-Lip 上调了处理的脂肪细胞中含有 16 (Prdm16) mRNA 水平的 PR 结构域。 α-Lip 促进来自超重/肥胖捐赠者的白色皮下脂肪细胞的线粒体生物发生和棕色样重塑 (C) 2014 Elsevier B.V. 保留所有权利。
alpha-Lipoic acid (alpha-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of alpha-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with alpha-Lip (100 and 250 mu M) for 24 h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes. The involvement of the Sirtuin1/Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (SIRT1/PGC-1 alpha) pathway was also evaluated. Our results showed that alpha-Lip increased mitochondrial content in cultured human adipocytes as revealed by electron microscopy and by mitotracker green labeling. Moreover, an enhancement in mtDNA content was observed. This increase was accompanied by an up-regulation of SIRT1 protein levels, a decrease in PGC-1 alpha acetylation and up-regulation of Nuclear respiratory factor 1 (Nrf1) and Mitochondria( transcription factor (Tfam) transcription factors. Enhanced oxygen consumption and fatty acid oxidation enzymes, Carnitine palmitoyl transferase 1 and Acyl-coenzyme A oxidase (CPT-1 and ACOX) were also observed. Mitochondria from alpha-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and alpha-Lip also induced up-regulation of some brown/beige adipocytes markers such as cell death-inducing DFFA-like effector a (Cidea) and T-box 1 (Tbx1). Moreover, alpha-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of alpha-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors. (C) 2014 Elsevier B.V. All rights reserved.