Ołdakowska Monika, Cierzniak Aneta, Jurek Tomasz, Małodobra-Mazur Małgorzata
Department of Forensic Medicine, Division of Molecular Techniques, Wroclaw Medical University, Sklodowskiej-Curie 52, 51-367 Wroclaw, Poland.
Genomtec S.A., Ul. Bierutowska 57-59, 51-317 Wroclaw, Poland.
Int J Mol Sci. 2025 Jul 31;26(15):7398. doi: 10.3390/ijms26157398.
Insulin resistance is a fundamental pathophysiological mechanism contributing to the development of type 2 diabetes and metabolic syndrome. Recently, attention has focused on mitochondria's role in glucose and lipid metabolism. Mitochondrial dysfunction is strongly associated with impaired energy metabolism and elevated oxidative stress. We investigated the mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in insulin-sensitive (IS) and insulin-resistant (IR) individuals. Twenty-seven paired adipose tissue biopsies were obtained during elective abdominal surgery. DNA and RNA were extracted, and mtDNA copy number was quantified using Real-Time PCR. We found that mtDNA content in VAT was approximately two-fold lower than in SAT. Furthermore, in IR individuals, mtDNA copy number was significantly reduced in both SAT and VAT compared to IS subjects. A strong positive correlation was observed between mtDNA content in VAT and body mass index (BMI), and a negative correlation was found with the QUICKI index. Additionally, mtDNA copy number in VAT positively correlated with the expression of several genes involved in insulin signalling, lipid metabolism, and other metabolic pathways. These findings underscore the central role of mitochondrial function in VAT in the context of metabolic disorders and suggest that targeting mitochondrial regulation in this tissue may represent a promising therapeutic approach.
胰岛素抵抗是导致2型糖尿病和代谢综合征发生的一种基本病理生理机制。最近，人们的注意力集中在线粒体在葡萄糖和脂质代谢中的作用。线粒体功能障碍与能量代谢受损和氧化应激升高密切相关。我们研究了胰岛素敏感（IS）和胰岛素抵抗（IR）个体皮下脂肪组织（SAT）和内脏脂肪组织（VAT）中的线粒体DNA（mtDNA）拷贝数。在择期腹部手术期间获取了27对脂肪组织活检样本。提取DNA和RNA，并使用实时PCR对mtDNA拷贝数进行定量。我们发现VAT中的mtDNA含量比SAT中的低约两倍。此外，与IS个体相比，IR个体的SAT和VAT中的mtDNA拷贝数均显著降低。在VAT中的mtDNA含量与体重指数（BMI）之间观察到强烈的正相关，而与QUICKI指数呈负相关。此外，VAT中的mtDNA拷贝数与参与胰岛素信号传导、脂质代谢和其他代谢途径的几个基因的表达呈正相关。这些发现强调了在代谢紊乱背景下VAT中线粒体功能的核心作用，并表明针对该组织中的线粒体调节可能是一种有前景的治疗方法。
