Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 11 2021
03 11 2021
Historique:
received:
23
04
2021
accepted:
15
10
2021
entrez:
4
11
2021
pubmed:
5
11
2021
medline:
28
1
2022
Statut:
epublish
Résumé
We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than WT-SkM, highlighted by a RAB35 decrease and an increase in intramuscular cholesterol content. Proteomic analyses of OB-ELVs revealed a group of 37 proteins functionally connected, involved in lipid oxidation and with catalytic activities. OB-ELVs had modified contents for phosphatidylcholine (PC 34-4, PC 40-3 and PC 34-0), sphingomyelin (Sm d18:1/18:1) and ceramides (Cer d18:1/18:0) and were enriched in cholesterol, likely to alleviated intracellular accumulation. Surprisingly many ELV miRNAs had a nuclear addressing sequence, and targeted genes encoding proteins with nuclear activities. Interestingly, SkM-ELV miRNA did not target mitochondria. The most significant function targeted by the 7 miRNAs altered in OB-ELVs was lipid metabolism. In agreement, OB-ELVs induced lipid storage in recipient adipocytes and increased lipid up-take and fatty acid oxidation in recipient muscle cells. In addition, OB-ELVs altered insulin-sensitivity and induced atrophy in muscle cells, reproducing the phenotype of the releasing OB muscles. These data suggest for the first time, a cross-talk between muscle cells and adipocytes, through the SkM-ELV route, in favor of adipose tissue expansion.
Identifiants
pubmed: 34732797
doi: 10.1038/s41598-021-00983-3
pii: 10.1038/s41598-021-00983-3
pmc: PMC8566600
doi:
Substances chimiques
Lipids
0
MicroRNAs
0
Muscle Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21626Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-10-INBS-08
Organisme : Agence Nationale de la Recherche
ID : ANR ZENITH n°45000260
Organisme : ANR
ID : ANR-17-EURE-0003
Informations de copyright
© 2021. The Author(s).
Références
Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5
pubmed: 11717410
J Lipid Res. 2018 Dec;59(12):2255-2261
pubmed: 29678958
J Extracell Vesicles. 2019 Dec 19;9(1):1703244
pubmed: 32002167
Prenat Diagn. 2005 Nov;25(11):1000-6
pubmed: 16231320
Cancer Res. 2016 Jul 15;76(14):4051-7
pubmed: 27216185
PLoS One. 2007 Sep 05;2(9):e851
pubmed: 17786222
Nat Cell Biol. 2007 Jun;9(6):654-9
pubmed: 17486113
Cold Spring Harb Perspect Biol. 2013 Oct 01;5(10):a016816
pubmed: 24086044
RNA Biol. 2010 Sep-Oct;7(5):606-14
pubmed: 20864815
Prostaglandins Leukot Essent Fatty Acids. 2011 Jan-Feb;84(1-2):7-11
pubmed: 21109411
Nat Cell Biol. 2008 Dec;10(12):1470-6
pubmed: 19011622
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17615-22
pubmed: 19822761
Theranostics. 2018 Mar 8;8(8):2171-2188
pubmed: 29721071
Diabetologia. 2016 May;59(5):1049-58
pubmed: 26852333
Int J Mol Sci. 2021 Feb 11;22(4):
pubmed: 33670146
Cytokine Growth Factor Rev. 2017 Feb;33:73-82
pubmed: 27765498
Prog Lipid Res. 2017 Apr;66:30-41
pubmed: 28342835
J Biol Chem. 2010 Jun 4;285(23):17442-52
pubmed: 20353945
Life Sci. 1987 Sep 7;41(10):1233-41
pubmed: 3041138
Science. 2007 Jan 5;315(5808):97-100
pubmed: 17204650
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
Cell Cycle. 2014;13(1):78-89
pubmed: 24196440
Springerplus. 2014 Oct 08;3:584
pubmed: 25332884
J Cell Biol. 2010 Apr 19;189(2):223-32
pubmed: 20404108
Front Immunol. 2014 Aug 20;5:403
pubmed: 25191326
J Diabetes Res. 2017;2017:1789395
pubmed: 28676863
Nat Commun. 2013;4:2980
pubmed: 24356509
RNA Biol. 2012 Mar;9(3):269-73
pubmed: 22336708
Gen Comp Endocrinol. 1971 Aug;17(1):164-82
pubmed: 5559131
Front Physiol. 2019 Aug 09;10:929
pubmed: 31447684
Bioinformatics. 2017 Jan 1;33(1):135-136
pubmed: 27605098
Proteomics. 2013 Aug;13(16):2419-23
pubmed: 23744604
Diabetologia. 1984 Sep;27(3):407-13
pubmed: 6238863
Science. 2012 May 18;336(6083):809-10
pubmed: 22605737
Obes Facts. 2018;11(4):294-305
pubmed: 30016792
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18957-62
pubmed: 17135348
Diabetes. 2018 Nov;67(11):2377-2388
pubmed: 29720498
Front Cell Dev Biol. 2019 May 03;7:70
pubmed: 31131274
Int J Obes (Lond). 2005 Oct;29(10):1175-83
pubmed: 16030519
Adipocyte. 2019 Dec;8(1):83-97
pubmed: 30905315
Biochem J. 2001 Nov 15;360(Pt 1):143-50
pubmed: 11696001
EMBO J. 2011 Aug 31;30(17):3481-500
pubmed: 21878991
J Clin Invest. 2004 Jan;113(1):115-23
pubmed: 14702115
Biochem Biophys Res Commun. 2002 Mar 1;291(3):701-6
pubmed: 11855847
Cell Res. 2012 Mar;22(3):504-15
pubmed: 21862971
J Biol Chem. 2003 May 16;278(20):18063-8
pubmed: 12621037
EMBO J. 2002 Mar 15;21(6):1289-300
pubmed: 11889035
Cell. 2005 Dec 16;123(6):1133-46
pubmed: 16337999
Cell. 2004 Jan 23;116(2):281-97
pubmed: 14744438
Proteomics. 2018 Mar;18(5-6):e1700375
pubmed: 29350465
RNA. 2011 Apr;17(4):675-86
pubmed: 21363885
Prostaglandins Leukot Essent Fatty Acids. 2018 Sep;136:161-169
pubmed: 28110829
Diabetologia. 2014 Oct;57(10):2155-64
pubmed: 25073444
Bioinformatics. 2020 May 1;36(10):3148-3155
pubmed: 32096818
Traffic. 2008 Feb;9(2):230-50
pubmed: 17999726
Front Mol Neurosci. 2013 Nov 26;6:43
pubmed: 24324399