Gene-chip studies of adipogenesis-regulated microRNAs in mouse primary adipocytes and human obesity (Affymetrix)

Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While the transcriptional program that initiates adipogenesis is well-known, the importance of microRNAs in adipogenesis is less well studied. We thus set out to investigate whether miRNAs would be actively modulated during adipogenesis and obesity. Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is probably the most well known, albeit not the most physiologically appropriate. We used a microarray strategy to provide a global profile of miRNAs in brown and white primary murine adipocytes (prior to and following differentiation) and evaluated the similarity of the responses to non-primary cell models, through literature data-mining. We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. When we compared our primary adipocyte profiles with those of cell lines reported in the literature, we found a high degree of difference in adipogenesis-regulated miRNAs. We evaluated the expression of 10 of our adipogenesis-regulated miRNAs using real-time qPCR and then selected 5 miRNAs that showed robust expression levels and profiled these by qPCR in subcutaneous adipose tissue of 20 humans with a range of body mass indices (BMI, range=21-48). Of the miRNAs tested, mir-21 was both highly expressed in human adipose tissue and positively correlated with BMI (R2=0.49, p<0.001). In conclusion, we provide the preliminary analysis of miRNAs important for primary cell in vitro adipogenesis and find that the inflammation-associated miRNA, mir-21, is up-regulated in subcutaneous adipose tissue in human obesity.

33

Keller P, Gburcik V, Petrovic N, Gallagher IJ, Nedergaard J, Cannon B, Timmons JA