Kaaman M, Sparks L M, van Harmelen V, Smith S R, Sjölin E, Dahlman I, Arner P
Karolinska Institute at Department of Medicine, Huddinge, Karolinska University Hospital, M61, Stockholm, Sweden.
Diabetologia. 2007 Dec;50(12):2526-33. doi: 10.1007/s00125-007-0818-6. Epub 2007 Sep 19.
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.
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.
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.
目的/假设：近期研究表明白色脂肪细胞中的胰岛素抵抗与线粒体功能之间存在联系。本研究旨在评估脂肪细胞线粒体DNA（mtDNA）拷贝数与脂肪细胞及与胰岛素敏感性相关的临床变量之间的关系。
我们研究了一组148名健康志愿者，他们的BMI存在较大个体差异。通过定量RT-PCR测定mtDNA和核DNA的相对含量。mtDNA与核DNA的比率反映了每个细胞中mtDNA的组织浓度。
mtDNA拷贝数在脂肪组织的脂肪细胞中富集，并随年龄增长（p = 0.015）和BMI增加（p = 0.004）而略有下降；然而，它不受性别、能量限制饮食或显著的长期体重减轻的影响。脂肪组织mtDNA拷贝数与静息能量消耗、总体胰岛素敏感性或脂肪细胞脂解无关。然而，它与脂肪细胞中的基础脂生成（p = 0.0012）和胰岛素刺激的脂生成（p < 0.0001）呈强正相关，独立于年龄和BMI，并且与参与线粒体氧化能力的几个基因的mRNA水平呈弱正相关（r = 0.2 - 0.3）。
结论/解读：健康个体中人类白色脂肪细胞的mtDNA拷贝数相当稳定。它不受性别或体重减轻的影响，对总体胰岛素敏感性或静息能量消耗也不重要。然而，它与脂肪细胞脂生成密切相关，与线粒体氧化能力呈弱相关，表明脂肪细胞线粒体首先是局部调节因子。
