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Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression

Margareta Jernås^*, Jenny Palming^*, Kajsa Sjöholm^*, Eva Jennische, Per-Arne Svensson^*, Britt G. Gabrielsson^*, Max Levin, Anders Sjögren, Mats Rudemo, Theodore C. Lystig^*, Björn Carlsson^*, Lena M. S. Carlsson^* and Malin Lönn^*,1

^* Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine,

Institute of Anatomy and Cell Biology, and

Cardiovascular Institute and Wallenberg Laboratory, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; and

Department of Mathematical Statistics, Chalmers University of Technology, Göteborg, Sweden

¹Correspondence: RCEM/Division of Body Composition and Metabolism, Department of Internal Medicine, Vita Stråket 15, SE 413 45 Göteborg, Sweden. E-mail: malin.lonn{at}medic.gu.se

ABSTRACT

Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6±3.54 µm) and large cells (mean 100.1±3.94 µm). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes. These genes may link hypertrophic obesity to insulin resistance/type 2 diabetes.—Jernås, M., Palming, J., Sjöholm, K., Jennische, E., Svensson, P.-A., Gabrielsson, B. G., Levin, M., Sjögren, A., Rudemo, M., Lystig, T. C., Carlsson, B., Carlsson, L. M. S., Lönn, M. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression.

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