Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue
Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue
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DOI：
10.1007/s00125-007-0818-6
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发表时间：
2007-12-01
期刊：
影响因子：
8.2
通讯作者：
Arner, P.
中科院分区：
文献类型：
--
作者：
Kaaman, M.;Sparks, L. M.;Arner, P.
目的/假设最近的研究表明胰岛素抵抗和白色脂肪细胞线粒体功能之间存在联系。本研究的目的是评估脂肪细胞线粒体DNA（mtDNA）的拷贝数与脂肪细胞和临床变量相关的胰岛素sensitivity.Methods我们研究了一组148名健康志愿者与一个大的个体间的差异BMI。用定量RT-PCR法测定线粒体DNA和核DNA的相对含量。mtDNA：结果脂肪组织中线粒体DNA拷贝数在脂肪细胞中富集，随增龄（p= 0.015）和BMI增加（p= 0.004）而略有下降，但不受性别、限能饮食和长期体重减轻的影响。脂肪mtDNA拷贝数与静息能量消耗、整体胰岛素敏感性或脂肪细胞脂解作用无关。然而，它与基础（p= 0.0012）和胰岛素刺激的脂肪生成（p< 0.0001）在脂肪细胞中，与年龄和BMI无关，与线粒体氧化能力相关的几个基因的mRNA水平呈弱正相关（r= 0.2 - 0.3）.结论/解释正常人白色脂肪细胞mtDNA拷贝数相当稳定。它不受性别或体重减轻的影响，对整体胰岛素敏感性或休息时的能量消耗也不重要。然而，它与脂肪细胞脂肪生成密切相关，与线粒体氧化能力弱相关，这表明脂肪细胞线粒体首先是局部调节剂。
Aims/hypothesis Recent studies suggest a link between insulin resistance and mitochondrial function in white fat cells. The aim of this study was to evaluate adipocyte mitochondrial DNA (mtDNA) copy number in relation to adipocyte and clinical variables that are related to insulin sensitivity.Methods We studied a group of 148 healthy volunteers with a large inter-individual variation in BMI. Relative amounts of mtDNA and nuclear DNA were determined by quantitative RT-PCR. The mtDNA: nuclear DNA ratio reflects the tissue concentration of mtDNA per cell.Results The mtDNA copy number was enriched in adipocytes of adipose tissue and decreased slightly by ageing (p= 0.015) and increasing BMI (p= 0.004); however, it was not influenced by sex, energy- restricted diets or marked long-term weight reduction. Adipose mtDNA copy number was not independently related to resting energy expenditure, overall insulin sensitivity or adipocyte lipolysis. However, it showed a strong positive correlation with basal (p= 0.0012) and insulin-stimulated lipogenesis (p< 0.0001) in fat cells, independently of age and BMI, and a weak positive correlation with levels of mRNA from several genes involved in mitochondrial oxidative capacity (r= 0.2 - 0.3).Conclusions/interpretation The mtDNA copy number in human white fat cells is fairly stable within healthy individuals. It is not influenced by sex or weight loss and is not important for overall insulin sensitivity or energy expenditure at rest. However, it is strongly related to adipocyte lipogenesis and weakly to mitochondrial oxidative capacity, suggesting that adipocyte mitochondria are, above all, local regulators.