Obesity related microRNA‑424 is regulated by TNF‑α in adipocytes.

Abstract

In recent years, obesity has become a major public health concern. Obesity has been previously associated with low‑grade inflammation and TNF‑α induction in adipose tissue, which subsequently disrupts adipocyte metabolism. MicroRNAs (miRNAs/miRs) are important metabolic factors and their dysregulation has been associated with obesity‑related metabolic syndromes. In fact, it has been directly suggested that miR‑424 may be functionally associated with adipogenesis, although its exact role in this process remains unclear. The present study aimed to identify the function of miR‑424 in adipogenesis. In the present study, miR‑424 expression levels were analyzed during adipogenesis and the differential expression of this miRNA in the adipose tissue of obese and non‑obese children was also assessed. Furthermore, the interaction between miR‑424 and the adipocytokine TNF‑α was determined. Finally, miR‑424 target genes and downstream signaling pathways were predicted via bioinformatics and analyzed by performing a luciferase reporter assay to elucidate the functional mechanisms of miR‑424 in adipogenesis of visceral adipocytes. The results revealed that the expression levels of miR‑424 upregulated in the adipose tissue biopsies from obese children compared with the biopsies of non‑obese children. However, in cultured adipocytes, the expression levels of miR‑424 were discovered to be gradually downregulated during the adipogenesis process. TNF‑α treatment significantly downregulated the expression levels of miR‑424 via binding to its promoter region and reducing its transcriptional activity. Through bioinformatic prediction analysis, miR‑424 target genes were analyzed, of which several were identified to be involved in signaling pathways that are known to regulate adipogenesis, such as the Wnt signaling pathway. In conclusion, the present study indicated that miR‑424 was regulated by TNF‑α and served an important role in adipogenesis.