miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression.
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.
Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, Baltimore, Maryland 21224, USA.
Eun Kyung
EK
Lee
Mi Jeong
MJ
Lee
Kotb
K
Abdelmohsen
Wook
W
Kim
Mihee M
MM
Kim
Subramanya
S
Srikantan
Jennifer L
JL
Martindale
Emmette R
ER
Hutchison
Hyeon Ho
HH
Kim
Bernard S
BS
Marasa
Roza
R
Selimyan
Josephine M
JM
Egan
Steven R
SR
Smith
Susan K
SK
Fried
Myriam
M
Gorospe
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics* / Q000502:physiology*; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013851:Thinness / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D012333:RNA, Messenger