Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum

Data on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quan...

Full description

Bibliographic Details
Main Authors: Martin Berghoff, Alexandra Höpfinger, Ranjithkumar Rajendran, Thomas Karrasch, Andreas Schmid, Andreas Schäffler
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/10/15/3271
_version_ 1797525467122630656
author Martin Berghoff
Alexandra Höpfinger
Ranjithkumar Rajendran
Thomas Karrasch
Andreas Schmid
Andreas Schäffler
author_facet Martin Berghoff
Alexandra Höpfinger
Ranjithkumar Rajendran
Thomas Karrasch
Andreas Schmid
Andreas Schäffler
author_sort Martin Berghoff
collection DOAJ
description Data on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quantified by ELISA in paired serum and CSF samples of 260 patients (107 males, 153 females) undergoing neurological evaluation. METRNL was abundant in serum (801.2 ± 378.3 pg/mL) and CSF (1007.2 ± 624.2 pg/mL) with a CSF/serum ratio of 1.4 ± 0.8. Serum METRNL levels were significantly correlated (rho = +0.521) to those in CSF. CSF METRNL concentrations were significantly correlated (rho = +0.480) with albumin CSF/serum ratios. The CSF/serum ratios of METRNL and albumin were positively correlated in Reibergram analysis (rho = 0.498), indicating that raising CSF concentrations of METRNL are mediated by increasing BBB dysfunction. The CSF concentrations of METRNL strongly increased in a stepwise manner along with increasing BBB dysfunction from grade 0 to grade 3 and with rising CSF cell count. CSF/serum ratio of METRNL also increased from grade 0 (1.2 ± 0.7) to grade 3 (3.0 ± 0.2). Furthermore, CSF levels were positively correlated with age. In conclusion, METRNL is a secreted and neurotrophic myokine that crosses over the BBB. CSF concentrations of METRNL increase with BBB dysfunction.
first_indexed 2024-03-10T09:14:19Z
format Article
id doaj.art-b194b0496a8a4ffba5c2e5a11ea002de
institution Directory Open Access Journal
issn 2077-0383
language English
last_indexed 2024-03-10T09:14:19Z
publishDate 2021-07-01
publisher MDPI AG
record_format Article
series Journal of Clinical Medicine
spelling doaj.art-b194b0496a8a4ffba5c2e5a11ea002de2023-11-22T05:48:21ZengMDPI AGJournal of Clinical Medicine2077-03832021-07-011015327110.3390/jcm10153271Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and SerumMartin Berghoff0Alexandra Höpfinger1Ranjithkumar Rajendran2Thomas Karrasch3Andreas Schmid4Andreas Schäffler5Department of Neurology, Giessen University Hospital, 35392 Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, 35392 Giessen, GermanyDepartment of Neurology, Giessen University Hospital, 35392 Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, 35392 Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, 35392 Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, 35392 Giessen, GermanyData on the quantification of the potentially neurotrophic adipo-myokine METRNL (Meteorin-like protein) in human cerebrospinal fluid (CSF) are lacking and migration of this secreted protein across the blood–brain barrier (BBB) is uncertain. In the present pilot study, METRNL concentrations were quantified by ELISA in paired serum and CSF samples of 260 patients (107 males, 153 females) undergoing neurological evaluation. METRNL was abundant in serum (801.2 ± 378.3 pg/mL) and CSF (1007.2 ± 624.2 pg/mL) with a CSF/serum ratio of 1.4 ± 0.8. Serum METRNL levels were significantly correlated (rho = +0.521) to those in CSF. CSF METRNL concentrations were significantly correlated (rho = +0.480) with albumin CSF/serum ratios. The CSF/serum ratios of METRNL and albumin were positively correlated in Reibergram analysis (rho = 0.498), indicating that raising CSF concentrations of METRNL are mediated by increasing BBB dysfunction. The CSF concentrations of METRNL strongly increased in a stepwise manner along with increasing BBB dysfunction from grade 0 to grade 3 and with rising CSF cell count. CSF/serum ratio of METRNL also increased from grade 0 (1.2 ± 0.7) to grade 3 (3.0 ± 0.2). Furthermore, CSF levels were positively correlated with age. In conclusion, METRNL is a secreted and neurotrophic myokine that crosses over the BBB. CSF concentrations of METRNL increase with BBB dysfunction.https://www.mdpi.com/2077-0383/10/15/3271myokineMETRNL (Meteorin-like protein)cerebrospinal fluidblood–brain barrieradipokine
spellingShingle Martin Berghoff
Alexandra Höpfinger
Ranjithkumar Rajendran
Thomas Karrasch
Andreas Schmid
Andreas Schäffler
Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
Journal of Clinical Medicine
myokine
METRNL (Meteorin-like protein)
cerebrospinal fluid
blood–brain barrier
adipokine
title Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
title_full Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
title_fullStr Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
title_full_unstemmed Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
title_short Evidence of a Muscle–Brain Axis by Quantification of the Neurotrophic Myokine METRNL (Meteorin-Like Protein) in Human Cerebrospinal Fluid and Serum
title_sort evidence of a muscle brain axis by quantification of the neurotrophic myokine metrnl meteorin like protein in human cerebrospinal fluid and serum
topic myokine
METRNL (Meteorin-like protein)
cerebrospinal fluid
blood–brain barrier
adipokine
url https://www.mdpi.com/2077-0383/10/15/3271
work_keys_str_mv AT martinberghoff evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum
AT alexandrahopfinger evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum
AT ranjithkumarrajendran evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum
AT thomaskarrasch evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum
AT andreasschmid evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum
AT andreasschaffler evidenceofamusclebrainaxisbyquantificationoftheneurotrophicmyokinemetrnlmeteorinlikeproteininhumancerebrospinalfluidandserum