Garufi Gabriella, Seyhan Attila A, Pasarica Magdalena
Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida, USA; Sanford Burnham Medical Research Institute, Orlando, Florida, USA.
Obesity (Silver Spring). 2015 Jan;23(1):24-7. doi: 10.1002/oby.20915. Epub 2014 Oct 16.
Rarefaction and inflammation of adipose tissue contributes to insulin resistance in obesity. It was hypothesized that angiostatic secreted frizzled-related protein 4 (SFRP4) causes adipose tissue rarefaction and leads to inflammation and ultimately insulin resistance in obese patients.
Abdominal subcutaneous adipose tissue (AbdAT), gluteal subcutaneous adipose tissue (GlutAT), and blood from 15 lean and obese subjects were collected. Circulating-SFRP4 was measured by ELISA. Body composition was measured by DEXA and insulin sensitivity by the euglycemic hyperinsulinemic clamp. Adipose tissue was analyzed using qRT-PCR for mRNA gene expression, Luminex system for tissue cytokine release, immunohistochemistry for labeling adipose capillaries, and osmium fixation and Coulter counting for adipocyte sizing.
Circulating-SFRP4 was higher in obese vs. lean subjects (137.8 ± 33.6 ng ml(-1) vs. 64.1 ± 23.8 ng ml(-1) , P < 0.05). Circulating-SFRP4 significantly (P < 0.05) correlated with body fat percentage (R = 0.07), body mass index (R = 0.07), insulin sensitivity (R = -0.66). Circulating-SFRP4 correlated with AbdAT-VEGF (R = -0.67, P < 0.05), AbdAT-capillary density (R = -0.65, P < 0.05), secreted-MIP1α (R = 0.74), and AbdAT-SFRP4 mRNA (R = 0.60). AbdAT-SFRP4 mRNA significantly correlated with AbdAT-capillary density (R = 0.71, P < 0.05), but not with AbdAT mean adipocyte size. There was no difference between AbdAT-SFRP4 and GlutAT-SFRP4 mRNA. Interestingly, GlutAT-SFRP4 correlated with AbdAT mean adipocyte size (P < 0.05).
The results suggested that AbdAT is a major contributor for circulating-SFRP4 and that SFRP4 has an important role in obese adipose tissue pathophysiology.
脂肪组织的萎缩和炎症会导致肥胖中的胰岛素抵抗。据推测，血管生成抑制性分泌型卷曲相关蛋白4（SFRP4）会导致脂肪组织萎缩，并引发炎症，最终导致肥胖患者出现胰岛素抵抗。
收集了15名瘦人和肥胖受试者的腹部皮下脂肪组织（AbdAT）、臀皮下脂肪组织（GlutAT）及血液。采用酶联免疫吸附测定法（ELISA）检测循环SFRP4。通过双能X线吸收法（DEXA）测量身体成分，通过正常血糖高胰岛素钳夹技术测量胰岛素敏感性。使用定量逆转录聚合酶链反应（qRT-PCR）分析脂肪组织的mRNA基因表达，采用Luminex系统检测组织细胞因子释放，通过免疫组织化学标记脂肪组织毛细血管，采用锇固定和库尔特计数法测量脂肪细胞大小。
肥胖受试者的循环SFRP4高于瘦人（137.8±33.6 ng/ml对64.1±23.8 ng/ml，P<0.05）。循环SFRP4与体脂百分比（R=0.07）、体重指数（R=0.07）、胰岛素敏感性（R=-0.66）显著相关（P<0.05）。循环SFRP4与AbdAT血管内皮生长因子（VEGF）（R=-0.67，P<0.05）、AbdAT毛细血管密度（R=-0.65，P<0.05）、分泌型巨噬细胞炎症蛋白1α（MIP1α）（R=0.74）及AbdAT-SFRP4 mRNA（R=0.60）相关。AbdAT-SFRP4 mRNA与AbdAT毛细血管密度显著相关（R=0.71，P<0.05），但与AbdAT平均脂肪细胞大小无关。AbdAT-SFRP4与GlutAT-SFRP4 mRNA之间无差异。有趣的是，GlutAT-SFRP4与AbdAT平均脂肪细胞大小相关（P<0.05）。
结果表明，AbdAT是循环SFRP4的主要来源，且SFRP4在肥胖脂肪组织病理生理学中起重要作用。
