Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany.
PLoS One. 2018 May 17;13(5):e0197603. doi: 10.1371/journal.pone.0197603. eCollection 2018.
Prolyl carboxypeptidase (PRCP) is involved in the regulation of body weight, likely by hydrolysing alpha-melanocyte-stimulating hormone and apelin in the hypothalamus and in the periphery. A link between PRCP protein concentrations in plasma and metabolic disorders has been reported. In this study, we investigated the distribution of circulating PRCP activity and assessed its relation with body weight and adipose tissue in obese patients and patients who significantly lost weight.
PRCP activity was measured using reversed-phase high-performance liquid chromatography in different isolated blood fractions and primary human cells to investigate the distribution of circulating PRCP. PRCP activity was measured in serum of individuals (n = 75) categorized based on their body mass index (BMI < 25.0; 25.0-29.9; 30.0-39.9; ≥ 40.0 kg/m2) and the diagnosis of metabolic syndrome. Differences in serum PRCP activity were determined before and six months after weight loss, either by diet (n = 45) or by bariatric surgery (n = 24). Potential correlations between serum PRCP activity and several metabolic and biochemical parameters were assessed. Additionally, plasma PRCP concentrations were quantified using a sensitive ELISA in the bariatric surgery group.
White blood cells and plasma contributed the most to circulating PRCP activity. Serum PRCP activity in lean subjects was 0.83 ± 0.04 U/L and increased significantly with a rising BMI (p<0.001) and decreased upon weight loss (diet, p<0.05; bariatric surgery, p<0.001). The serum PRCP activity alteration reflected body weight changes and was found to be positively correlated with several metabolic parameters, including: total, abdominal and visceral adipose tissue. Plasma PRCP concentration was found to be significantly correlated to serum PRCP activity (0.865; p<0.001). Additionally, a significant decrease (p<0.001) in plasma PRCP protein concentration (mean ± SD) before (18.2 ± 3.7 ng/mL) and 6 months after bariatric surgery (15.7 ± 2.7 ng/mL) was found.
Our novel findings demonstrate that white blood cells and plasma contributed the most to circulating PRCP activity. Additionally, we have shown that there were significant correlations between serum PRCP activity and various metabolic parameters, and that plasma PRCP concentration was significantly correlated to serum PRCP activity. These novel findings on PRCP activity in serum support further investigation of its in vivo role and involvement in several metabolic diseases.
脯氨酰羧肽酶(PRCP)参与体重调节,可能通过水解下丘脑和外周的α-黑色素细胞刺激素和apelin。已经报道了血浆 PRCP 蛋白浓度与代谢紊乱之间的联系。在这项研究中,我们研究了循环 PRCP 活性的分布,并评估了其与肥胖患者和体重显著减轻患者的体重和脂肪组织的关系。
使用反相高效液相色谱法在不同的分离血液成分和原代人细胞中测量 PRCP 活性,以研究循环 PRCP 的分布。根据身体质量指数(BMI<25.0;25.0-29.9;30.0-39.9;≥40.0 kg/m2)和代谢综合征的诊断,对 75 名个体的血清中的 PRCP 活性进行分类。通过饮食(n=45)或减肥手术(n=24)测量减肥前后血清 PRCP 活性的差异。评估血清 PRCP 活性与多种代谢和生化参数之间的潜在相关性。此外,在减肥手术组中使用敏感 ELISA 定量测定血浆 PRCP 浓度。
白细胞和血浆对循环 PRCP 活性的贡献最大。瘦受试者的血清 PRCP 活性为 0.83±0.04 U/L,随着 BMI 的升高而显著增加(p<0.001),并在减肥后降低(饮食,p<0.05;减肥手术,p<0.001)。血清 PRCP 活性的变化反映了体重变化,并与多种代谢参数呈正相关,包括:总、腹部和内脏脂肪组织。发现血浆 PRCP 浓度与血清 PRCP 活性显著相关(0.865;p<0.001)。此外,还发现减肥手术后(18.2±3.7ng/mL)与减肥手术前(15.7±2.7ng/mL)相比,血浆 PRCP 蛋白浓度显著降低(p<0.001)。
我们的新发现表明,白细胞和血浆对循环 PRCP 活性的贡献最大。此外,我们还表明,血清 PRCP 活性与多种代谢参数之间存在显著相关性,并且血浆 PRCP 浓度与血清 PRCP 活性显著相关。这些关于血清中 PRCP 活性的新发现支持进一步研究其在体内的作用及其与多种代谢疾病的关系。