miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor γ expression

Eun Kyung Lee, Mi Jeong Lee, Kotb Abdelmohsen, Wook Kim, Mihee M. Kim, Subramanya Srikantan, Jennifer L. Martindale, Emmette R. Hutchison, Hyeon Ho Kim, Bernard S. Marasa, Roza Selimyan, Josephine M. Egan, Steven R. Smith, Susan K. Fried, Myriam Gorospe

Research output: Contribution to journalArticlepeer-review

313 Scopus citations

Abstract

Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong posttranscriptional 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 γ (PPARγ), a major regulator of adipogenesis. Interestingly, miR-130 potently repressed PPARγ expression by targeting both the PPARγ mRNA coding and 3′ untranslated regions. Adipose tissue from obese women contained significantly lower miR-130 and higher PPARγ mRNA levels than that from nonobese women. Our findings reveal that miR-130 reduces adipogenesis by repressing PPARγ biosynthesis and suggest that perturbations in this regulation is linked to human obesity.

Original languageEnglish
Pages (from-to)626-638
Number of pages13
JournalMolecular and Cellular Biology
Volume31
Issue number4
DOIs
StatePublished - Feb 2011
Externally publishedYes

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