PMID- 29772029 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 5 DP - 2018 TI - Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects. PG - e0197603 LID - 10.1371/journal.pone.0197603 [doi] LID - e0197603 AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. FAU - Kehoe, Kaat AU - Kehoe K AUID- ORCID: 0000-0001-7412-4960 AD - Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Noels, Heidi AU - Noels H AD - Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany. FAU - Theelen, Wendy AU - Theelen W AD - Institute for Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany. FAU - De Hert, Emilie AU - De Hert E AD - Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Xu, Shenguan AU - Xu S AD - Section of Clinical Chemistry, Department of Medical Sciences, University of Uppsala, Uppsala, Sweden. FAU - Verrijken, An AU - Verrijken A AD - Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium. AD - Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. FAU - Arnould, Thierry AU - Arnould T AD - Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium. FAU - Fransen, Erik AU - Fransen E AD - StatUa Center for Statistics, University of Antwerp, Antwerp, Belgium. FAU - Hermans, Nina AU - Hermans N AD - Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Lambeir, Anne-Marie AU - Lambeir AM AD - Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Venge, Per AU - Venge P AD - Section of Clinical Chemistry, Department of Medical Sciences, University of Uppsala, Uppsala, Sweden. FAU - Van Gaal, Luc AU - Van Gaal L AD - Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium. AD - Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. FAU - De Meester, Ingrid AU - De Meester I AD - Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180517 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - EC 3.4.- (Carboxypeptidases) RN - EC 3.4.16.2 (lysosomal Pro-X carboxypeptidase) SB - IM MH - Adipose Tissue/*chemistry MH - Adult MH - Anthropometry MH - Aorta MH - Bariatric Surgery MH - Blood Cells/enzymology MH - *Body Weight MH - Carboxypeptidases/*blood MH - Diet, Reducing MH - Endothelial Cells/enzymology MH - Female MH - Humans MH - Macrophages/enzymology MH - Male MH - Middle Aged MH - Myocytes, Smooth Muscle/enzymology MH - Obesity/diet therapy/*enzymology/surgery MH - Plasma/enzymology MH - Platelet Activation MH - Platelet-Rich Plasma/enzymology MH - Thinness/*enzymology MH - Weight Loss PMC - PMC5957431 COIS- The authors have declared that no competing interests exist. EDAT- 2018/05/18 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/05/17 CRDT- 2018/05/18 06:00 PHST- 2017/06/06 00:00 [received] PHST- 2018/05/04 00:00 [accepted] PHST- 2018/05/18 06:00 [entrez] PHST- 2018/05/18 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/05/17 00:00 [pmc-release] AID - PONE-D-17-21643 [pii] AID - 10.1371/journal.pone.0197603 [doi] PST - epublish SO - PLoS One. 2018 May 17;13(5):e0197603. doi: 10.1371/journal.pone.0197603. eCollection 2018.