Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity.
IGF-1R
endothelium
microbiota
obesity
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 05 2021
05 05 2021
Historique:
revised:
12
03
2021
received:
28
04
2020
accepted:
22
03
2021
pubmed:
3
5
2021
medline:
1
6
2021
entrez:
2
5
2021
Statut:
ppublish
Résumé
Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are critical for coupling nutritional status and cellular growth; IGF-1R is expressed in multiple cell types including EC. The role of ECIGF-1R in the response to nutritional obesity is unexplored. To examine this, we use gene-modified mice with EC-specific overexpression of human IGF-1R (hIGFREO) and their wild-type littermates. After high-fat feeding, hIGFREO weigh less, have reduced adiposity and have improved glucose tolerance. hIGFREO show an altered gene expression and altered microbial diversity in the gut, including a relative increase in the beneficial genus Akkermansia. The depletion of gut microbiota with broad-spectrum antibiotics induces a loss of the favourable metabolic differences seen in hIGFREO mice. We show that IGF-1R facilitates crosstalk between the EC and the gut wall; this crosstalk protects against diet-induced obesity, as a result of an altered gut microbiota.
Identifiants
pubmed: 33934497
doi: 10.15252/embr.202050767
pmc: PMC8097321
doi:
Substances chimiques
Receptor, IGF Type 1
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e50767Subventions
Organisme : Medical Research Council
ID : MR/R014086/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/13/1/30086
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/59/34896
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/12/80/29821
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/15/7/31521
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/18/82/34120
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SI/14/1/30718
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/14/54/30939
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/44/33792
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U2C DK092993
Pays : United States
Organisme : NIH HHS
ID : U24-DK092993
Pays : United States
Organisme : Diabetes UK
ID : 16/0005382
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
Références
Science. 2018 Aug 10;361(6402):599-603
pubmed: 30093598
Diabetes. 2011 Aug;60(8):2169-78
pubmed: 21677284
Clin Endocrinol (Oxf). 2015 May;82(5):704-11
pubmed: 25040157
Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6
pubmed: 23193283
Nat Commun. 2012;3:1245
pubmed: 23212374
J Obes. 2016;2016:7353642
pubmed: 27703805
PLoS One. 2014 Jul 22;9(7):e102252
pubmed: 25050889
Int J Endocrinol. 2018 Mar 22;2018:4095789
pubmed: 29849617
Diabetes. 2012 Sep;61(9):2359-68
pubmed: 22733797
Cell. 2007 Aug 24;130(4):691-703
pubmed: 17719546
Diab Vasc Dis Res. 2019 Mar;16(2):160-170
pubmed: 30295509
Nat Med. 2017 Jan;23(1):107-113
pubmed: 27892954
Cell Mol Life Sci. 2000 Jul;57(7):1050-93
pubmed: 10961344
Front Microbiol. 2017 Sep 22;8:1765
pubmed: 29018410
Nat Rev Immunol. 2020 Feb;20(2):91-92
pubmed: 31768024
Endocrinology. 2019 Jun 1;160(6):1506-1514
pubmed: 31070724
Nat Med. 2019 Jul;25(7):1096-1103
pubmed: 31263284
Diabetes Res Clin Pract. 2014 Feb;103(2):137-49
pubmed: 24630390
Gut. 2016 Mar;65(3):426-36
pubmed: 26100928
FEMS Immunol Med Microbiol. 2005 Aug 1;45(2):183-9
pubmed: 15939578
Nature. 2006 Dec 21;444(7122):1027-31
pubmed: 17183312
Circulation. 2019 May 28;139(22):2570-2584
pubmed: 30922063
Gastroenterology. 2012 Oct;143(4):913-6.e7
pubmed: 22728514
Gut. 2018 Feb;67(2):271-283
pubmed: 28377388
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
J Neurosci. 2011 Jun 15;31(24):8998-9009
pubmed: 21677183
Circ Res. 2018 Oct 12;123(9):1015-1016
pubmed: 30355167
Nat Methods. 2016 Jul;13(7):581-3
pubmed: 27214047
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23
pubmed: 15505215
Science. 2015 Oct 30;350(6260):558-63
pubmed: 26516283
Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R211-6
pubmed: 27252473
Clin Endocrinol (Oxf). 2015 Dec;83(6):834-41
pubmed: 25866162
Cell Metab. 2014 Jan 7;19(1):96-108
pubmed: 24411942
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7554-E7563
pubmed: 27821775
Eur J Nutr. 2012 Oct;51(7):861-70
pubmed: 22042005
Biogerontology. 2017 Dec;18(6):913-929
pubmed: 28795262
Physiol Rev. 2015 Jul;95(3):727-48
pubmed: 26084689
Microb Ecol Health Dis. 2015 May 29;26:27663
pubmed: 26028277
Postgrad Med J. 2016 May;92(1087):286-300
pubmed: 26912499
Circulation. 2020 Jul 28;142(4):365-379
pubmed: 32393053
J Biomed Sci. 2019 Aug 21;26(1):59
pubmed: 31434568
PLoS One. 2014 Dec 23;9(12):e115922
pubmed: 25535951
N Engl J Med. 1996 Oct 31;335(18):1363-7
pubmed: 8857020
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):9731-9736
pubmed: 28827363
Magn Reson Med. 2013 Jul;70(1):155-9
pubmed: 22887356
PLoS One. 2010 Mar 10;5(3):e9490
pubmed: 20224823
Endocr Rev. 1995 Feb;16(1):3-34
pubmed: 7758431
Endocrinology. 2014 Feb;155(2):370-9
pubmed: 24265452
Molecules. 2019 Nov 05;24(21):
pubmed: 31694161
ISME J. 2011 Feb;5(2):169-72
pubmed: 20827291
Nature. 2010 Nov 11;468(7321):310-5
pubmed: 21068842
BMC Microbiol. 2016 Nov 8;16(1):264
pubmed: 27821063
Nat Commun. 2018 Jul 18;9(1):2802
pubmed: 30022049
Int J Syst Evol Microbiol. 2004 Sep;54(Pt 5):1469-1476
pubmed: 15388697
Front Microbiol. 2017 Nov 22;8:2306
pubmed: 29213261
Lancet Diabetes Endocrinol. 2014 Nov;2(11):901-10
pubmed: 24731669
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4592-8
pubmed: 20937873
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71
pubmed: 23671105
Nat Biotechnol. 2019 Aug;37(8):852-857
pubmed: 31341288
Diabetes. 2017 Nov;66(11):2808-2821
pubmed: 28830894
Diabetes. 2017 Feb;66(2):287-299
pubmed: 28108607
EMBO Rep. 2021 May 5;22(5):e50767
pubmed: 33934497
N Engl J Med. 2016 Dec 15;375(24):2369-2379
pubmed: 27974040