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

Journal article
Authors Margareta Jernås
Jenny Palming
Kajsa Sjöholm
Eva Jennische
Per-Arne Svensson
Britt G. Gabrielsson
Max Levin
Anders Sjögren
Mats Rudemo
Ted Lystig
Björn Carlsson
Lena M S Carlsson
Malin Lönn
Published in The FASEB Journal
Volume 20
Pages E832–E839
ISSN 1530-6860
Publication year 2006
Published at Wallenberg Laboratory
Department of Mathematical Sciences, Mathematical Statistics
Institute of Health and Care Sciences
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages E832–E839
Language en
Links dx.doi.org/10.1096/fj.05-5678fje
Keywords cell size, serum amyloid a, transmembrane 4 L six family member 1, leptin, insulin resistance
Subject categories Mathematical statistics, Endocrinology

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 um) and large cells (mean 100.1+-3.94 um). 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.

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