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

BMC Endocrine Disorders

James A Timmons¹  Barbara Cannon¹  Jan Nedergaard¹  Iain J Gallagher³  Natasa Petrovic¹  Valentina Gburcik²  Pernille Keller⁴ 

[1] Department of Physiology, The Wenner-Gren Institute, Stockholm University, Sweden;Royal Veterinary College, University of London, UK;Tissue Injury & Repair Group, The Chancellor's Building, University of Edinburgh, EH16 4SB, UK;Department of Molecular Genetics, Novo Nordisk A/S, DK-2760 Måløv Denmark

关键词: transcriptome;    Adipose tissue: adipocyte;    Affymetrix;    EXIQON;    microarray;    microRNAs;    primary white and brown adipocytes;   

Others  :  1086571
DOI  :  10.1186/1472-6823-11-7

 received in 2010-10-05, accepted in 2011-03-22,  发布年份 2011

【 摘 要 】

Background

Adipose tissue abundance relies partly on the factors that regulate adipogenesis, i.e. proliferation and differentiation of adipocytes. While components of 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.

Methods

Several models exist to study adipogenesis in vitro, of which the cell line 3T3-L1 is the most well known, albeit not the most physiologically appropriate. Thus, as an alternative, we produced EXIQON microarray of brown and white primary murine adipocytes (prior to and following differentiation) to yield global profiles of miRNAs.

Results

We found 65 miRNAs regulated during in vitro adipogenesis in primary adipocytes. We evaluated the similarity of our responses to those found in non-primary cell models, through literature data-mining. When comparing primary adipocyte profiles, with those of cell lines reported in the literature, we found a high degree of difference in 'adipogenesis' regulated miRNAs suggesting that the model systems may not be accurately representing adipogenesis. The expression of 10 adipogenesis-regulated miRNAs were studied using real-time qPCR and then we selected 5 miRNAs, that showed robust expression, were profiled in subcutaneous adipose tissue obtained from 20 humans with a range of body mass indices (BMI, range = 21-48, and all samples have U133+2 Affymetrix profiles provided). Of the miRNAs tested, mir-21 was robustly expressed in human adipose tissue and positively correlated with BMI (R2 = 0.49, p < 0.001).

Conclusion

In conclusion, we provide a preliminary analysis of miRNAs associated with primary cell in vitro adipogenesis and demonstrate that the inflammation-associated miRNA, mir-21 is up-regulated in subcutaneous adipose tissue in human obesity. Further, we provide a novel transcriptomics database of EXIQON and Affymetrix adipocyte profiles to facilitate data mining.

【 授权许可】

   
2011 Keller et al; licensee BioMed Central Ltd.

【 图 表 】

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