Wang Ran, Zhou Wei, Zhu Xiaolei, Zhou Nan, Yang Fan, Sun Bin, Li Xiaonan
Department of Children Health Care, Children's Hospital of Nanjing Medical University , Nanjing, China.
Department of General Surgery, Children's Hospital of Nanjing Medical University , Nanjing, China.
Endocr Res. 2020 Aug;45(3):190-201. doi: 10.1080/07435800.2020.1721528. Epub 2020 Jan 27.
To observe the expression of Nrg4, uncoupling protein-1 (UCP1), tumor necrosis factor α (TNFα), CD31, VE-cadherin/CDH5 and vascular endothelial growth factor A (VEGF-A) mRNA in abdominal subcutaneous (SC), omental (OM) adipose tissue in children with relation to anthropometric parameters. Further to verify the effect of inflammatory mediators on Nrg4 and UCP1 mRNA expression in adipocytes.
Paired SC and OM adipose tissues were obtained from 58 children. In vitro, the adipocytes isolated from primary inguinal adipose tissue of mice were treated with TNFα (50 ng/ml) for 12-48 h. mRNA levels of Nrg4, UCP1 and TNFα were determined by real-time PCR.
Nrg4, UCP1, VEGF-A and CDH5 mRNA levels in SC were significantly higher than those in OM adipose tissue and the mRNA level of TNFα showed the opposite result. Moreover, Nrg4 and UCP1 mRNA in SC were significantly lower in overweight children compared to normal weight children. Nrg4 in SC and OM was negatively associated with BMISDS, WHtR. CDH55 mRNA in OM was negatively associated with WHR. VEGF-A was positively correlated with Nrg4 in SC. In vitro, Nrg4 and UCP1 mRNA levels in adipocytes were dose- and time-dependently decreased under TNFα treatment.
Nrg4, UCP1, VEGF-A and CDH5 mRNA expression in adipose tissues display a depot-specific pattern. Nrg4 mRNA levels in adipose tissue are decreased with obesity and associated with WAT browning and angiogenesis. TNFα may be involved in the regulation of Nrg4 level in adipose tissue, which may be one of the causes of the down-regulation of Nrg4 expression in obesity with chronic inflammatory response.
观察儿童腹部皮下（SC）、网膜（OM）脂肪组织中神经调节蛋白4（Nrg4）、解偶联蛋白-1（UCP1）、肿瘤坏死因子α（TNFα）、CD31、血管内皮钙黏蛋白/CDH5和血管内皮生长因子A（VEGF-A）mRNA的表达与人体测量参数的关系。进一步验证炎症介质对脂肪细胞中Nrg4和UCP1 mRNA表达的影响。
从58名儿童获取配对的SC和OM脂肪组织。在体外，将从小鼠原代腹股沟脂肪组织分离的脂肪细胞用TNFα（50 ng/ml）处理12 - 48小时。通过实时PCR测定Nrg4、UCP1和TNFα的mRNA水平。
SC中Nrg4、UCP1、VEGF-A和CDH5的mRNA水平显著高于OM脂肪组织，而TNFα的mRNA水平则相反。此外，超重儿童SC中的Nrg4和UCP1 mRNA明显低于正常体重儿童。SC和OM中的Nrg4与体重指数标准差评分（BMISDS）、腰高比（WHtR）呈负相关。OM中的CDH5 mRNA与腰臀比（WHR）呈负相关。VEGF-A与SC中的Nrg4呈正相关。在体外，TNFα处理下脂肪细胞中Nrg4和UCP1 mRNA水平呈剂量和时间依赖性降低。
脂肪组织中Nrg4、UCP1、VEGF-A和CDH5 mRNA表达呈现特定部位模式。脂肪组织中Nrg4 mRNA水平随肥胖而降低，并与白色脂肪组织棕色化和血管生成相关。TNFα可能参与脂肪组织中Nrg4水平的调节，这可能是肥胖伴慢性炎症反应时Nrg4表达下调的原因之一。
