High levels of modified ceramides are a defining feature of murine and human cancer cachexia.

Animals Cachexia / etiology Ceramides / metabolism Humans Mice Muscular Atrophy Neoplasms / complications Quality of Life
Cancer cachexia Ceramides Lipidomics Signalling lipids Sphingolipids

Journal

Journal of cachexia, sarcopenia and muscle
ISSN: 2190-6009
Titre abrégé: J Cachexia Sarcopenia Muscle
Pays: Germany
ID NLM: 101552883

Informations de publication

Date de publication:
12 2020
Historique:
received: 06 07 2020
accepted: 19 08 2020
pubmed: 23 10 2020
medline: 26 10 2021
entrez: 22 10 2020
Statut: ppublish

Résumé

Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients. Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss. High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.

Sections du résumé

BACKGROUND
Cancer cachexia (CCx) is a multifactorial energy-wasting syndrome reducing the efficiency of anti-cancer therapies, quality of life, and survival of cancer patients. In the past years, most studies focused on the identification of tumour and host-derived proteins contributing to CCx. However, there is still a lack of studies addressing the changes in bioactive lipids. The aim of this study was to identify specific lipid species as a hallmark of CCx by performing a broad range lipid analysis of plasma from well-established CCx mouse models as well as cachectic and weight stable cancer patients.
METHODS
Plasma from non-cachectic (PBS-injected mice, NC26 tumour-bearing mice), pre-cachectic and cachectic mice (C26 and LLC tumour-bearing mice, Apc
RESULTS
A decrease in several lysophosphatidylcholine (LPC) species and an increase in numerous sphingolipids including sphingomyelins (SMs), ceramides (CERs), hexosyl-ceramides (HCERs) and lactosyl-ceramides (LCERs), were mutual features of CCx in both mice and cancer patients. Notably, sphingolipid levels gradually increased during cachexia development. Key enzymes involved in ceramide synthesis were elevated in liver but not in adipose, muscle, or tumour tissues, suggesting that ceramide turnover in the liver is a major contributor to elevated sphingolipid levels in CCx. LPC(16:1), LPC(20:3), SM(16:0), SM(24:1), CER(16:0), CER(24:1), HCER(16:0), and HCER(24:1) were the most consistently affected lipid species between mice and humans and correlated negatively (LPCs) or positively (SMs, CERs and HCERs) with the severity of body weight loss.
CONCLUSIONS
High levels of sphingolipids, specifically ceramides and modified ceramides, are a defining feature of murine and human CCx and may contribute to tissue wasting and skeletal muscle atrophy through the inhibition of anabolic signals. The progressive increase in sphingolipids during cachexia development supports their potential as early biomarkers for CCx.

Identifiants

DOI: 10.1002/jcsm.12626 PMID: 33090732 PMC: PMC7749558
pubmed: 33090732
doi: 10.1002/jcsm.12626
pmc: PMC7749558
doi:

Substances chimiques

Ceramides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1459-1475

Subventions

Organisme : Austrian Science Fund FWF
ID : J 4224
Pays : Austria

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

Références

Oncotarget. 2019 Oct 15;10(57):5983-5992
pubmed: 31666929
J Cachexia Sarcopenia Muscle. 2019 Oct;10(5):1143-1145
pubmed: 31661195
Biochim Biophys Acta. 2011 Dec;1812(12):1601-6
pubmed: 21914473
Adv Nutr. 2015 Sep 15;6(5):513-40
pubmed: 26374175
Br J Cancer. 2009 Mar 10;100(5):713-22
pubmed: 19259092
Oncogenesis. 2016 Jan 25;5:e189
pubmed: 26807644
Trends Cancer. 2018 Dec;4(12):849-860
pubmed: 30470306
Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E423-35
pubmed: 27382035
Br J Cancer. 2004 Mar 8;90(5):996-1002
pubmed: 14997196
J Nutr. 2010 Oct;140(10):1774-80
pubmed: 20739445
Metabolomics. 2018;14(6):72
pubmed: 29805336
Nat Med. 2017 May;23(5):631-637
pubmed: 28346411
J Vet Med. 2015;2015:152730
pubmed: 26464949
Lipids Health Dis. 2019 Jan 26;18(1):29
pubmed: 30684960
Br J Cancer. 1998 Jun;77(11):1978-83
pubmed: 9667678
Eur J Clin Nutr. 2012 Mar;66(3):399-404
pubmed: 22234041
Oncotarget. 2018 Apr 13;9(28):19874-19890
pubmed: 29731990
Lancet Oncol. 2011 May;12(5):489-95
pubmed: 21296615
J Clin Oncol. 2006 Jul 20;24(21):3401-7
pubmed: 16849754
J Lipid Res. 2008 May;49(5):1137-46
pubmed: 18281723
Cell. 2014 Oct 9;159(2):318-32
pubmed: 25303528
Skelet Muscle. 2012 Jan 18;2(1):2
pubmed: 22257771
J Cachexia Sarcopenia Muscle. 2020 Dec;11(6):1459-1475
pubmed: 33090732
Pharmacol Ther. 2019 Apr;196:117-134
pubmed: 30521881
Clin Nutr. 2008 Dec;27(6):793-9
pubmed: 18718696
Curr Opin Clin Nutr Metab Care. 2012 May;15(3):246-51
pubmed: 22366922
J Clin Oncol. 2004 Jun 15;22(12):2469-76
pubmed: 15197210
Lipids Health Dis. 2007 Jul 10;6:17
pubmed: 17623088
Adv Exp Med Biol. 2019;1159:109-138
pubmed: 31502202
Nat Rev Cancer. 2020 May;20(5):274-284
pubmed: 32235902
J Crit Care. 2014 Oct;29(5):882.e5-11
pubmed: 24961965
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Aug;1862(8):747-751
pubmed: 28238863
Science. 1990 Jan 19;247(4940):322-4
pubmed: 2296722
Trends Mol Med. 2019 Jan;25(1):20-32
pubmed: 30477968
Aging Cell. 2019 Apr;18(2):e12915
pubmed: 30719830
Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494
pubmed: 29762782
Cell Metab. 2015 Aug 4;22(2):266-278
pubmed: 26190650
Science. 2019 Jul 26;365(6451):386-392
pubmed: 31273070
J Cachexia Sarcopenia Muscle. 2017 Apr;8(2):190-201
pubmed: 27897400
Metabolomics. 2018 Sep 20;14(10):128
pubmed: 30830398
Cancers (Basel). 2019 Oct 19;11(10):
pubmed: 31635032
Sci Rep. 2016 Feb 05;6:20391
pubmed: 26847922
Anal Chem. 2014 Oct 7;86(19):9662-9
pubmed: 25160652
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Cell. 2011 Sep 30;147(1):173-84
pubmed: 21962514
FASEB J. 2005 Oct;19(12):1719-21
pubmed: 16051685
Semin Cell Dev Biol. 2016 Jun;54:53-67
pubmed: 26593326
PLoS One. 2014 Jan 17;9(1):e85724
pubmed: 24465667
Cell Metab. 2014 Oct 7;20(4):678-86
pubmed: 25295788
Horm Mol Biol Clin Investig. 2014 Aug;19(2):117-28
pubmed: 25390020
J Lipid Res. 2003 Apr;44(4):754-61
pubmed: 12562829
Sci Rep. 2017 Sep 27;7(1):12348
pubmed: 28955042
J Oncol. 2012;2012:254801
pubmed: 23319946
Nat Rev Endocrinol. 2018 Dec;15(1):9-20
pubmed: 30464312
Clin Nutr ESPEN. 2018 Jun;25:18-25
pubmed: 29779814
FEBS Lett. 2015 Oct 24;589(21):3221-7
pubmed: 26434718
J Cachexia Sarcopenia Muscle. 2012 Mar;3(1):5-11
pubmed: 22450024
Front Nutr. 2020 Jan 31;7:4
pubmed: 32083092
Biochem J. 2017 Jul 27;474(16):2663-2678
pubmed: 28751550
Nature. 2013 Oct 24;502(7472):550-4
pubmed: 24153306
J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):348-357
pubmed: 29464940

Auteurs

Pauline Morigny (P)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Julia Zuber (J)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Mark Haid (M)

Research Unit Molecular Endocrinology and Metabolism, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.

Doris Kaltenecker (D)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Fabien Riols (F)

Research Unit Molecular Endocrinology and Metabolism, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.

Joanna D C Lima (JDC)

Cancer Metabolism Research Group, LIM 26 HC, Medical School, University of São Paulo, São Paulo, Brazil.

Estefania Simoes (E)

Cancer Metabolism Research Group, LIM 26 HC, Medical School, University of São Paulo, São Paulo, Brazil.

José Pinhata Otoch (JP)

Cancer Metabolism Research Group, LIM 26 HC, Medical School, University of São Paulo, São Paulo, Brazil.

Sören Fisker Schmidt (SF)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.

Stephan Herzig (S)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
Molecular Metabolic Control, Technical University of Munich, Munich, Germany.

Jerzy Adamski (J)

Research Unit Molecular Endocrinology and Metabolism, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Experimentelle Genetik, Technical University of Munich, Freising-Weihenstephan, Neuherberg, Germany.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Marilia Seelaender (M)

Cancer Metabolism Research Group, LIM 26 HC, Medical School, University of São Paulo, São Paulo, Brazil.

Mauricio Berriel Diaz (M)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
ORCID: 0000-0003-4670-919X

Maria Rohm (M)

Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
ORCID: 0000-0003-3926-1534

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › High levels of modified ceramides are a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Cachexie › High levels of modified ceramides are a...
questionsmedicales.fr › Lipides › Lipides membranaires › Sphingolipides › Glycosphingolipides › Glycosphingolipides neutres › Céramides › High levels of modified ceramides are a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › High levels of modified ceramides are a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › High levels of modified ceramides are a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Manifestations neuromusculaires › Amyotrophie › High levels of modified ceramides are a...
questionsmedicales.fr › Tumeurs › High levels of modified ceramides are a...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Démographie › État de santé › Qualité de vie › High levels of modified ceramides are a...