Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression.
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 microm) and large cells (mean 100.1+/-3.94 microm). 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
Margareta
M
Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita Stråket 15, SE 413 45 Göteborg, Sweden.
Palming
Jenny
J
Sjöholm
Kajsa
K
Jennische
Eva
E
Svensson
Per-Arne
PA
Gabrielsson
Britt G
BG
Levin
Max
M
Sjögren
Anders
A
Rudemo
Mats
M
Lystig
Theodore C
TC
Carlsson
Björn
B
Carlsson
Lena M S
LM
Lönn
Malin
M
D017667:Adipocytes / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D048429:Cell Size; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000235:genetics / Q000502:physiology; D008297:Male; D017698:Postmenopause; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020738:Leptin