microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma.
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 PPARgamma and C/EBPalpha, two key regulators of adipogenesis, during early onset of adipogenesis and repressed adipogenic marker gene expression and triglyceride accumulation at late stages. PPARgamma 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 PPARgamma.
Karbiener
Michael
M
Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse 14, 8010 Graz, Austria.
Fischer
Christoph
C
Nowitsch
Susanne
S
Opriessnig
Peter
P
Papak
Christine
C
Ailhaud
Gerard
G
Dani
Christian
C
Amri
Ez-Zoubir
EZ
Scheideler
Marcel
M
D020413:3' Untranslated Regions / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D022763:CCAAT-Enhancer-Binding Protein-alpha; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma