microRNA miR-27b impairs human adipocyte differentiation and targets PPAR gamma

作者:Karbiener Michael; Fischer Christoph; Nowitsch Susanne; Opriessnig Peter; Papak Christine; Ailhaud Gerard; Dani Christian; Amri Ez Zoubir; Scheideler Marcel*
来源:Biochemical and Biophysical Research Communications, 2009, 390(2): 247-251.
DOI:10.1016/j.bbrc.2009.09.098

摘要

Obesity has emerged as a global health problem with more than 1.1 billion adults to be classified as overweight or obese, and is associated with type 2 diabetes, cardiovascular disease, and several cancers. Since obesity is characterized by an increased size and/or number of adipocytes, elucidating the molecular events governing adipogenesis is of utmost importance. Recent findings indicate that microRNAs (miRNAs) - small non-protein-coding RNAs that function as post-transcriptional gene regulators - are involved in the regulatory network of adipogenesis. Whereas only a single human miRNA is known so far to be functional in adipogenesis as pro-adipogenic, several mouse miRNAs have been identified very recently as adipogenic regulators, thereby stimulating demand for studying the functional role of miRNAs during adipogenesis in human. Here, we demonstrate that miR-27b abundance decreased during adipogenesis of human multipotent adipose-derived stem (hMADS) cells. Overexpression of miR-27b blunted induction of PPAR gamma and C/EBP alpha, two key regulators of adipogenesis, during early onset of adipogenesis and repressed adipogenic marker gene expression and triglyceride accumulation at late stages. PPAR gamma has a predicted and highly conserved binding site in its 3'UTR and was indeed confirmed to be a direct target of miR-27b. Thus, these results suggest that the anti-adipogenic effect of miR-27b in hMADS cells is due, at least in part, to suppression of PPAR gamma.

  • 出版日期2009-12-11