SFRP2 Is Associated with Increased Adiposity and VEGF Expression.
OBJECTIVE
The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance.


METHODS
Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed.


RESULTS
sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed.


CONCLUSIONS
Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression.
St Vincent's University Hospital & University College Dublin, Dublin, Ireland.
Rachel K
RK
Crowley
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Michael W
http://orcid.org/0000-0002-9108-9105
MW
O'Reilly
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Iwona J
IJ
Bujalska
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Zaki K
ZK
Hassan-Smith
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Jonathan M
JM
Hazlehurst
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Danielle R
DR
Foucault
University of Leeds School of Medicine, Leeds LS2 9NL, United Kingdom.
Paul M
PM
Stewart
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom.
Jeremy W
JW
Tomlinson
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