Integrative Analysis of Exosomal miR-452 and miR-4713 Downregulating NPY1R for the Prevention of Childhood Obesity

Abstract

Neuropeptides are associated with childhood obesity and exploring their regulatory mechanisms may reveal new insights for novel treatments. Childhood obesity data were downloaded from the GEO database and were used to screen for differentially expressed neuropeptides in patients with obesity. NPY1R expression was significantly upregulated in children with obesity compared to children without obesity ( $p<0.05$ ). The GEO database was used to filter differentially expressed miRNAs in patients with obesity. And hsa-mir-4713 and hsa-mir-452 were found significantly downregulated in adipose tissue. The GEO, TRRUST, and TFacts databases were used to screen all transcription factors for differentially expressed genes (DEGs). The potential regulatory networks between the differentially expressed miRNAs, TFs, and neuropeptides were mapped. In the constructed NPY1R regulatory network, the transcription factors TCF4, HEY1, and GATA3 are significantly associated with NPY1R. TCF4 and HEY1 were positively correlated with NPY1R, while GATA3 was negatively correlated with NPY1R. In the clinical peripheral blood samples, NPY1R, TCF4, and HEY1 were significantly more expressed in the obesity and the obesity with fracture group compared to the control group, while there was no statistically significant difference between the obesity group and the obesity with fracture group in terms of expression. The expression of GATA3, miR-452, and miR-4713 was also significantly lower in the obesity and the obesity with fracture groups when compared to the NC group. Therefore, NPY1R, TCF4, HEY1, GATA3, miR-452, and miR-4713 may be risk factors for fracture in obese children. The potential NPY1R regulatory function was exerted by two pathways: positive regulation caused by TCF4 and HEY1 acting on miR-4713 and negative regulation via GATA3 acting on miR-452. Potential NPY1R-related targets for the treatment of childhood obesity were provided in this study.