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Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity

International Journal of Obesity volume 35, pages 1154–1164 (2011)Cite this article

Subjects

Abstract

Objective:

Insulin resistance and type 2 diabetes mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. In this study, we identified the underlying molecular processes in preadipocytes of T2DM patients, a characteristic for the development of T2DM.

Design and Participants:

Preadipocyte cell cultures were prepared from subcutaneous fat biopsies of seven T2DM patients (age 53±12 years; body mass index (BMI) 34±5 kg m–2) and nine control subjects (age 51±12 years; BMI 30±3 kg m–2). Microarray analysis was used to identify altered processes between the T2DM and control preadipocytes.

Results:

Gene expression profiling showed changed expression of transcription regulators involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were downregulated, and inflammation/apoptosis was upregulated in T2DM preadipocytes.

Conclusion:

Decreased expression of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.

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Acknowledgements

We thank Martin Wabitsch for kindly providing the SGBS cells, Glaxo Smith Kline for kindly providing Rosiglitazone and the Microarray Facility Utrecht for providing the oligonucleotide microarrays. The research presented was funded by the Dutch Diabetes Foundation (DFN 2004.00.040).

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Authors and Affiliations

  1. Department of Genetics and Cell Biology, Maastricht University, Maastricht, The Netherlands

    F H J van Tienen, P J Lindsey & H J M Smeets

  2. School for Nutrition, Toxicology and Metabolism of Maastricht University Medical Centre (NUTRIM), Maastricht University, Maastricht, The Netherlands

    F H J van Tienen, P J Lindsey & H J M Smeets

  3. Cardiovasculair Research Institute Maastricht (CARIM), Maastricht, University, Maastricht, The Netherlands

    C J H van der Kallen, P J Lindsey, M M van Greevenbroek & H J M Smeets

  4. Department of Internal Medicine, Laboratory of Molecular Metabolism and Endocrinology, Maastricht University, Maastricht, The Netherlands

    C J H van der Kallen & M M van Greevenbroek

  5. GROW-School of Oncology & Developmental Biology, Maastricht, University, Maastricht, The Netherlands

    P J Lindsey & H J M Smeets

  6. Departments of Clinical Chemistry and Pediatrics, Laboratory Genetic, Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    R J Wanders

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Correspondence to H J M Smeets.

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van Tienen, F., van der Kallen, C., Lindsey, P. et al. Preadipocytes of type 2 diabetes subjects display an intrinsic gene expression profile of decreased differentiation capacity. Int J Obes 35, 1154–1164 (2011). https://doi.org/10.1038/ijo.2010.275

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  • DOI: https://doi.org/10.1038/ijo.2010.275

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