MiR-1275 Inhibits Human Omental Adipose-Derived Stem Cells Differentiation Toward the Beige Phenotype via PRDM16.

Abstract

Beige adipocytes have recently attracted attention for their potential as new therapeutic targets in the management of obesity and related metabolic disorders. MicroRNAs (miRNAs) have been reported as transcriptional regulators or biomarkers of brown and beige adipogenesis. Nevertheless, the effects of miRNAs involved in beige differentiation of human visceral adipocytes remain to be investigated. In this study, microarray screening showed that miR-1275 was significantly decreased during the differentiation of beige adipocytes induced by human omental adipose-derived stem cells (hASCs). Overexpression of miR-1275 suppressed the "brown-like" differentiation of hASCs by inhibiting the key transcriptional factor PR domain containing 16 (PRDM16) without affecting the proliferation. Adipogenesis and mitochondrial biogenesis of beige adipocytes derived from hASCs were impaired by miR-1275 overexpression. The regulatory effect of miR-1275 was determined by direct binding to the 3'-untranslated region of PRDM16, which was demonstrated by a dual-luciferase assay. Taken together, this study identified miR-1275 as a negative regulator of beige cell development in hASCs by inhibiting PRDM16. Thus, miR-1275 might be a potential target in the management of visceral obesity and related metabolic diseases.