Cell-specific dysregulation of microRNA expression in obese white adipose tissue.
BACKGROUND
Obesity is characterized by the excessive accumulation of dysfunctional white adipose tissue (WAT), leading to a strong perturbation of metabolic regulations. However, the molecular events underlying this process are not fully understood.


OBJECTIVE
MicroRNAs (miRNAs) are small noncoding RNAs acting as posttranscriptional regulators of gene expression in multiple tissues and organs. However, their expression and roles in WAT cell subtypes, which include not only adipocytes but also immune, endothelial, and mesenchymal stem cells as well as preadipocytes, have not been characterized. Design/Results: By applying differential miRNome analysis, we demonstrate that the expression of several miRNAs is dysregulated in epididymal WAT from ob/ob and high-fat diet-fed mice. Adipose tissue-specific down-regulation of miR-200a and miR-200b and the up-regulation of miR-342-3p, miR-335-5p, and miR-335-3p were observed. Importantly, a similarly altered expression of miR-200a and miR-200b was observed in obese diabetic patients. Furthermore, cell fractionation of mouse adipose tissue revealed that miRNAs are differentially expressed in adipocytes and in subpopulations from the stromal vascular fraction. Finally, integration of transcriptomic data showed that bioinformatically predicted miRNA target genes rarely showed anticorrelated expression with that of targeting miRNA, in contrast to experimentally validated target genes.


CONCLUSIONS
Taken together, our data indicate that the dysregulated expression of miRNAs occurs in distinct cell types and is likely to affect cell-specific function(s) of obese WAT.
European Genomic Institute for Diabetes (F.O., C.G., D.M., Y.B., O.M.-C., E.B., S.C., D.D., F.P., H.D., J.E., B.S., P.L.), Inserm Unité Mixte de Recherche Unité 1011 (F.O., C.G., D.M., Y.B., O.M.-C., E.B., S.C., D.D., H.D., J.E., B.S., P.L.), Université Lille 2 (F.O., C.G., D.M., Y.B., O.M.-C., E.B., S.C., D.D., F.P., H.D., J.E., B.S., P.L.), and Inserm Unité Mixte de Recherche Unité 859 (F.P.), F-59000 Lille, France; Institut Pasteur de Lille (F.O., C.G., D.M., Y.B., O.M.-C., E.B., S.C., D.D., H.D., J.E., B.S., P.L.), F-59019 Lille, France; and Centre Hospitalier Régional Universitaire de Lille (F.P.), F-59045, Lille, France.
Frédérik
F
Oger
Celine
C
Gheeraert
Denis
D
Mogilenko
Yacir
Y
Benomar
Olivier
O
Molendi-Coste
Emmanuel
E
Bouchaert
Sandrine
S
Caron
David
D
Dombrowicz
François
F
Pattou
Hélène
H
Duez
Jérome
J
Eeckhoute
Bart
B
Staels
Philippe
P
Lefebvre
D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics
D035683:MicroRNAs