Abstract
Prochemerin is the inactive precursor of the adipokine chemerin. Proteolytic processing is obligatory for the conversion of prochemerin into active chemerin and subsequent regulation of cellular processes via the chemokine-like receptor 1 (CMKLR1). Elevated plasma or serum chemerin concentrations and differential processing of prochemerin have been reported in obese humans. The impact of these changes on CMKLR1 signalling in humans is unknown. The objective of this pilot study was to develop a cellular bioassay to measure CMKLR1 activation by chemerin present in human serum and to characterise how obesity modifies serum activation of CMKLR1 under fasted and fed conditions. Blood samples were collected from control (N = 4, BMI 20-25) and obese (N = 4, BMI >30) female subjects after an overnight fast (n = 2) and at regular intervals (n = 7) following consumption of breakfast over a period of 6 h. A cellular CMKLR1-luminescent reporter assay and a pan-chemerin ELISA were used to determine CMKLR1 activation and total chemerin concentrations, respectively. Serum total chemerin concentration (averaged across all samples) was higher in obese vs control subjects (17.9 ± 1.8 vs 10.9 ± 0.5 nM, P < 0.05), but serum activation of CMKLR1 was similar in both groups. The CMKLR1 activation/total chemerin ratio was lower in obese vs control subjects (0.33 ± 0.04 vs 0.58 ± 0.05, P < 0.05). After breakfast, serum total chemerin or CMKLR1 activation did not differ from baseline values. In conclusion, the unexpected observation that obese serum activation of CMKLR1 did not match increased total chemerin concentrations suggests impaired processing to and/or enhanced degradation of active chemerin in serum of obese humans.
| Original language | English |
|---|---|
| Pages (from-to) | 70-81 |
| Number of pages | 12 |
| Journal | Endocrine Connections |
| Volume | 5 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Nov 1 2016 |
Bibliographical note
Funding Information:The authors express their sincere thanks to the subjects who volunteered their time to participate in the clinical study. They would like to sincerely thank Catherine Brown (Clinical Operations Coordinator, Canadian Centre for Vaccinology) and her staff for organising and conducting the clinical sampling procedures. They are grateful to Nichole McMullen, Dr Alexandra Roman and Yan Wang for their assistance with technical aspects of the project and Dr Gilad Barnea (Brown University) who provided the HTLA cells and the CMKLR1-tTA expression plasmids that were used in the CMKLR1 bioassay.
Publisher Copyright:
© 2016 The authors Published by Bioscientifica Ltd.
ASJC Scopus Subject Areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology
