Institute for Sustainability & Food Chain Innovation (ISFOOD), Navarra Institute for Health Research (IdiSNA), Department of Health Sciences, Public University of Navarra, Pamplona, Spain.
TECNALIA, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Alava, Miñano, Spain.
Pediatr Obes. 2022 Dec;17(12):e12966. doi: 10.1111/ijpo.12966. Epub 2022 Aug 31.
miRNA have been proposed as potential biomarkers of metabolic diseases.
To identify potential miRNA biomarkers of early metabolic-associated fatty liver disease (MAFLD) and/or insulin resistance (IR) in preadolescent children.
A total of 70 preadolescents, aged 8.5-12 years old participated in the study. Hepatic fat was assessed by magnetic resonance imaging. Fasting blood biochemical parameters were measured and HOMA-IR calculated. Peripheral blood mononuclear cells (PBMC)-derived miRNA profiles associated with MAFLD (≥5.5% hepatic fat) and IR (HOMA-IR ≥2.5) were identified using untargeted high-throughput miRNAs sequencing (RNA-seq).
A total of 2123 PBMC-derived miRNAs were identified in children with (21.4%) or without MAFLD. Among them, hsa-miR-143-3p, hsa-miR-142-5p and hsa-miR-660-5p were up-regulated, and p-hsa-miR-247, hsa-let-7a-5p and hsa-miR-6823-3p down-regulated. Importantly, children with MAFLD had consistently higher miR-660-5p expression levels than their peers without it (p < 0.01), regardless of weight status. A total of 2124 PBMC-derived miRNA were identified in children with IR (28.6%) versus children without IR, where thirteen of them were dysregulated (p < 0.05) in children with IR. In addition, children with IR showed higher levels of miR-374a-5p and miR-190a-5p (p < 0.01) and lower levels of miR-4284 and miR-4791 (p < 005), than their peers without IR in both the whole sample and in those with overweight or obesity.
Our study results suggest circulating miR-660-5p as a potential biomarker of the presence of MAFLD in preadolescent children while circulating miR-320a, miR-142-3p, miR-190a-5p, miR-374a-5p and let-7 family miRNAs could serve as potential biomarkers of IR in children.
miRNA 被认为是代谢疾病的潜在生物标志物。
鉴定青少年前期代谢相关脂肪性肝病（MAFLD）和/或胰岛素抵抗（IR）的潜在 miRNA 生物标志物。
共纳入 70 名 8.5-12 岁的青少年。通过磁共振成像评估肝脂肪含量。测量空腹血生化参数并计算 HOMA-IR。使用非靶向高通量 miRNA 测序（RNA-seq）鉴定与 MAFLD（≥5.5%肝脂肪）和 IR（HOMA-IR≥2.5）相关的 PBMC 衍生 miRNA 谱。
在有（21.4%）或无 MAFLD 的儿童中，共鉴定出 2123 种 PBMC 衍生 miRNA。其中，hsa-miR-143-3p、hsa-miR-142-5p 和 hsa-miR-660-5p 上调，p-hsa-miR-247、hsa-let-7a-5p 和 hsa-miR-6823-3p 下调。重要的是，无论体重状态如何，患有 MAFLD 的儿童的 miR-660-5p 表达水平始终高于无 MAFLD 的同龄人（p<0.01）。在有 IR（28.6%）的儿童与无 IR 的儿童中，共鉴定出 2124 种 PBMC 衍生 miRNA，其中 13 种在有 IR 的儿童中失调（p<0.05）。此外，与无 IR 的同龄人相比，有 IR 的儿童的 miR-374a-5p 和 miR-190a-5p 水平更高（p<0.01），miR-4284 和 miR-4791 水平更低（p<005），无论他们是否超重或肥胖。
我们的研究结果表明，循环 miR-660-5p 可作为青少年前期 MAFLD 存在的潜在生物标志物，而循环 miR-320a、miR-142-3p、miR-190a-5p、miR-374a-5p 和 let-7 家族 miRNA 可作为儿童 IR 的潜在生物标志物。
