Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Universidad de Málaga, Campus Teatinos s/n - 29010, Málaga, Spain.
Unidad de Gestión Clinica de Endocrinologia y Nutricion, Instituto de Investigacion Biomedica de Malaga (IBIMA), Hospital Universitario Virgen de la Victoria, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Málaga, Spain.
Obesity (Silver Spring). 2019 Feb;27(2):245-254. doi: 10.1002/oby.22363. Epub 2018 Dec 30.
This study aimed to analyze the potential association of different microRNA (miRNA) molecules with both type 2 diabetes (T2D) and obesity and determine their target genes.
Quantitative PCR was used to analyze the miR-20b, miR-296, and Let-7f levels in human visceral and subcutaneous adipose tissues (ATs) in relation to obesity and T2D, miRTarBase 4.0 was used for validation of target genes, and the Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System and the Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to annotate the biological processes of the predicted targets.
In AT, miR-20b, miR-296, and Let-7f levels were significantly different between normoglycemic subjects and those with T2D. In visceral adipose tissue, miRNA levels were higher in normoglycemic/obesity samples than in T2D/obesity samples. miR-20b-miR-296 and Let-7f target genes that showed significant differences in both ATs in relation to obesity and T2D were CDKN1A, CX3CL1, HIF1A, PPP2R1B, STAT3, and VEGFA. These genes are known to be principally involved in the vascular endothelial growth factor (VEGF) and WNT pathways.
This study provides experimental evidence of the possible correlation between AT miR-20b-miR-296-Let-7f with obesity and T2D, which might involve vascular endothelial growth factor and WNT-dependent pathways that are regulated by six different genes, suggesting a novel signaling pathway that could be important for understanding the mechanisms underlying the AT dysfunction associated with obesity and T2D.
本研究旨在分析不同微小 RNA（miRNA）分子与 2 型糖尿病（T2D）和肥胖的潜在关联，并确定其靶基因。
采用定量 PCR 分析了人内脏和皮下脂肪组织（AT）中 miR-20b、miR-296 和 Let-7f 水平与肥胖和 T2D 的关系，使用 miRTarBase 4.0 验证靶基因，使用蛋白质分析通过进化关系（PANTHER）分类系统和注释、可视化和综合发现数据库（DAVID）注释预测靶标的生物学过程。
在 AT 中，miR-20b、miR-296 和 Let-7f 水平在血糖正常受试者和 T2D 受试者之间存在显著差异。在内脏脂肪组织中，miRNA 水平在血糖正常/肥胖样本中高于 T2D/肥胖样本。miR-20b-miR-296 和 Let-7f 的靶基因在肥胖和 T2D 相关的两种 AT 中差异显著，包括 CDKN1A、CX3CL1、HIF1A、PPP2R1B、STAT3 和 VEGFA。这些基因主要参与血管内皮生长因子（VEGF）和 WNT 途径。
本研究为 AT miR-20b-miR-296-Let-7f 与肥胖和 T2D 之间可能存在相关性提供了实验证据，这可能涉及血管内皮生长因子和 WNT 依赖途径，受六个不同基因调节，提示了一个新的信号通路，可能对理解与肥胖和 T2D 相关的 AT 功能障碍的机制具有重要意义。
