miR-130 Suppresses Adipogenesis by Inhibiting Peroxisome Proliferator-Activated Receptor γ Expression

Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong post-transcriptional regulators of mammalian differentiation. We hypothesized that microRNAs might influence human adipogenesis by targeting specific adipogenic factors. We identified microRNAs that showed varying abundance during the differentiation of human preadipocytes into adipocytes. Among them, miR-130 strongly affected adipocyte differentiation, as overexpressing miR-130 impaired adipogenesis and reducing miR-130 enhanced adipogenesis. A key effector of miR-130 actions was the protein peroxisome proliferator-activated receptor gamma (PPAR gamma), a major regulator of adipogenesis. Interestingly, miR-130 potently repressed PPAR gamma expression by targeting both the PPAR gamma mRNA coding and 3' untranslated regions. Adipose tissue from obese women contained significantly lower miR-130 and higher PPAR gamma mRNA levels than that from nonobese women. Our findings reveal that miR-130 reduces adipogenesis by repressing PPAR gamma biosynthesis and suggest that perturbations in this regulation is linked to human obesity.