SFRP2 Is Associated with Increased Adiposity and VEGF Expression.

SFRP2 Is Associated with Increased Adiposity and VEGF Expression.
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DOI:
10.1371/journal.pone.0163777
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Tomlinson JW
Tomlinson JW
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Crowley RK;O'Reilly MW;Bujalska IJ;Hassan-Smith ZK;Hazlehurst JM;Foucault DR;Stewart PM;Tomlinson JW

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本研究的目的是评估脂肪组织分泌的卷曲相关蛋白2(SFRP2)的库特异性表达和分泌及其对脂肪细胞生物学的影响。我们在体内检测了106例患者的血清SFRP2浓度,以探讨其与脂肪量、血糖和胰岛素抵抗的关系。用聚合酶链式反应和Western印迹法检测SFRP2在小鼠和人组织中的表达。Western印迹证实脂肪组织分泌SFRP2进入细胞培养液。检测重组SFRP2对脂肪生成和前脂肪细胞增殖的影响。检测重组SFRP2暴露后前脂肪细胞血管内皮生长因子(VEGF)和活化T细胞核因子3(NFATc3)的表达。此外,还进行了与年龄、性别、肥胖和胰岛素分泌相关的补充性临床研究。小鼠和人脂肪组织中均有SFRP2信使RNA的表达。在人类中,大网膜中SFRP2mRNA的表达是皮下脂肪的4.2倍。大眼脂肪组织比皮下组织多分泌63%的SFRP2蛋白。重组SFRP2处理不影响脂肪生成或前脂肪细胞的增殖,但与增加VEGFmRNA的表达有关。在受试者中,循环胰岛素水平与血清SFRP2水平呈正相关,糖耐量异常患者的水平(34.2 ng/ml)高于对照组(29.5 ng/ml)。SFRP2与BMI呈正相关。循环中的SFRP2与脂肪组织质量有关,并可能通过增强血管内皮生长因子的表达而促进脂肪血管的生成。
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. 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. 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. Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression.
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