Markina Natalia O, Matveev Georgy A, Zasypkina Ksenia A, Khromova Natalia V, Babenko Alina Yu, Shlyakhto Evgeny V
Science Department of Metabolic Deviations and Personalized Prevention, Almazov National Medical Research Centre, St. Petersburg 197341, Russia.
Int J Mol Sci. 2025 Aug 24;26(17):8212. doi: 10.3390/ijms26178212.
Metabolically healthy (MHO) and unhealthy obesity (MUO) exhibit distinct molecular genetic mechanisms underlying metabolic disorders. Studying gene and microRNA expression in subcutaneous adipose tissue (SAT) may reveal key pathogenetic differences between these phenotypes. We compared the expression of genes (ADIPOQ, HIF1A, CCL2) and microRNAs (miR-142-3p, miR-155, miR-378) in SAT between MHO and MUO patients and assessed their association with metabolic parameters. The study included 39 obese patients (19 MHO, 20 MUO) and 10 healthy controls. SAT biopsies were analyzed using real-time PCR. Correlations with clinical and metabolic markers were evaluated. Obese patients showed decreased ADIPOQ ( = 0.039) and miR-142 ( = 0.008) expression and increased CCL2 ( = 0.004), miR-155 ( = 0.017), and miR-378 ( = 0.04) expression compared to the controls. MUO patients exhibited higher HIF1A expression ( = 0.03) and strong correlations between CCL2 and dyslipidemia (total cholesterol, triglycerides)/dysglycemia (fasting glucose) (r = 0.45, = 0.03; r = 0.52, = 0.01; r = 0.63, = 0.001, respectively). miR-142 negatively correlated with fibrosis markers, while miR-378 was linked to insulin resistance. The differential gene and microRNA expression highlights the role of inflammation, hypoxia, and fibrosis in MUO pathogenesis. miR-142-3p, miR-155, and miR-378 may serve as potential biomarkers for metabolic risk stratification and therapeutic targets.
代谢健康型肥胖(MHO)和代谢不健康型肥胖(MUO)在代谢紊乱方面表现出不同的分子遗传机制。研究皮下脂肪组织(SAT)中的基因和微小RNA表达可能揭示这些表型之间关键的致病差异。我们比较了MHO和MUO患者SAT中基因(ADIPOQ、HIF1A、CCL2)和微小RNA(miR - 142 - 3p、miR - 155、miR - 378)的表达,并评估了它们与代谢参数的关联。该研究纳入了39名肥胖患者(19名MHO,20名MUO)和10名健康对照。使用实时PCR分析SAT活检样本。评估了与临床和代谢标志物的相关性。与对照组相比,肥胖患者的ADIPOQ(P = 0.039)和miR - 142(P = 0.008)表达降低,CCL2(P = 0.004)、miR - 155(P = 0.017)和miR - 378(P = 0.04)表达升高。MUO患者表现出更高的HIF1A表达(P = 0.03),并且CCL2与血脂异常(总胆固醇、甘油三酯)/血糖异常(空腹血糖)之间存在强相关性(r分别为0.45,P = 0.03;r = 0.52,P = 0.01;r = 0.63,P = 0.001)。miR - 142与纤维化标志物呈负相关,而miR - 378与胰岛素抵抗有关。基因和微小RNA的差异表达突出了炎症、缺氧和纤维化在MUO发病机制中的作用。miR - 142 - 3p、miR - 155和miR - 378可能作为代谢风险分层的潜在生物标志物和治疗靶点。