Hossein-Nezhad A, Mirzaei K, Ansar H, Emam-Gholipour S, Tootee A, Keshavarz S A
Endocrinology and Metabolism Research Institute, Tehran University of Medical SciencesTehran, Iran.
Minerva Endocrinol. 2012 Sep;37(3):255-66.
The aim of the study was to measure circulating PGRN levels and to investigate its potential correlation with resting metabolic rate and obesity related complications. Moreover, to investigate on the PGRN and some important gene expressions in energy expenditure in vitro in samples of PBMCs derived from all participants of our study in a cellular model.
Of the 163 participants who were recruited for the current cross-sectional study, 37 (22.69%) were normal weight (18.5≤BMI<25), 53 (32.51%) were overweight (25≤BMI<30), 48 (29.44%) were categorized as class I obese (BMI 30 -34.9) and 25 (15.33%) were classified as class II and III obese (BMI≥35). All participants were assessed for the measurement of RMR by means of indirect calorimetry following an overnight fasting. Body composition was analyzed with the Bioelectrical Impedance technique by the BODY COMPOSITION ANALYZER BC-418M -Tanita. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using specific primer pairs for PGRN, AKT, MAPK and mRNA, and beta actin mRNA was used as the internal control. Circulating PGRN was measured with the use of ELISA method.
The circulating levels and gene expressions of PGRN rose in parallel with the increase of body weight. However, there was significant difference in the strength of association between circulating PGRN as well as PGRN gene expression and obesity-related variables. Moreover, PGRN gene expression had significant correlation with BMI, visceral fat, MAPK and AKT gene expression. The increased mass of visceral fat in correlation with the increased PGRN levels was more pronounced in high or normal resting metabolic rate group compared with the group with low resting metabolic rate. After adjusting for BMI and gender, we found that circulating PGRN can predict the RMR/kg independent of other variables such as TG, HDL, and hs-CRP (P=0.03).
PGRN associated with obesity and glucose homeostasis and may predict the resting metabolic rate levels independent of confounder factors. Experimental study may clarify the PGRN role in obesity etiology through metabolism regulation.
本研究旨在测量循环中前颗粒蛋白（PGRN）水平，并探讨其与静息代谢率及肥胖相关并发症之间的潜在关联。此外，在细胞模型中，研究本研究所有参与者外周血单个核细胞（PBMC）样本中PGRN及一些与能量消耗相关重要基因的表达情况。
在本次横断面研究招募的163名参与者中，37名（22.69%）体重正常（18.5≤体重指数（BMI）<25），53名（32.51%）超重（25≤BMI<30），48名（29.44%）被归类为I级肥胖（BMI 30 - 34.9），25名（15.33%）被归类为II级和III级肥胖（BMI≥35）。所有参与者在过夜禁食后通过间接测热法评估静息代谢率（RMR）。使用百利达BC - 418M人体成分分析仪通过生物电阻抗技术分析身体成分。通过Ficoll - 泛影葡胺技术从全血中分离PBMC。提取总细胞RNA并合成cDNA。随后使用针对PGRN、AKT、丝裂原活化蛋白激酶（MAPK）和信使核糖核酸（mRNA）的特异性引物对进行实时聚合酶链反应（PCR），并以β - 肌动蛋白mRNA作为内参。使用酶联免疫吸附测定（ELISA）法测量循环中的PGRN。
PGRN的循环水平和基因表达随体重增加而平行升高。然而，循环PGRN以及PGRN基因表达与肥胖相关变量之间的关联强度存在显著差异。此外，PGRN基因表达与BMI、内脏脂肪、MAPK和AKT基因表达显著相关。与低静息代谢率组相比，高或正常静息代谢率组中，内脏脂肪量增加与PGRN水平升高的相关性更为明显。在调整BMI和性别后，我们发现循环PGRN可独立于甘油三酯（TG）、高密度脂蛋白（HDL）和高敏C反应蛋白（hs - CRP）等其他变量预测每千克体重的RMR（P = 0.03）。
PGRN与肥胖和葡萄糖稳态相关，可能独立于混杂因素预测静息代谢率水平。实验研究可能通过代谢调节阐明PGRN在肥胖病因学中的作用。
