Ghrelin Signaling: GOAT and GHS-R1a Take a LEAP in Complexity.
GHS-R1a
GPCR dimers
LEAP2
diabetes
energy balance
ghrelin
ghrelin O-acyltransferase
obesity
Journal
Trends in endocrinology and metabolism: TEM
ISSN: 1879-3061
Titre abrégé: Trends Endocrinol Metab
Pays: United States
ID NLM: 9001516
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
06
08
2019
revised:
25
09
2019
accepted:
27
09
2019
pubmed:
23
10
2019
medline:
4
8
2021
entrez:
23
10
2019
Statut:
ppublish
Résumé
Ghrelin and the growth hormone secretagogue receptor 1a (GHS-R1a) are important targets for disorders related to energy balance and metabolic regulation. Pharmacological control of ghrelin signaling is a promising avenue to address health issues involving appetite, weight gain, obesity, and related metabolic disorders, and may be an option for patients suffering from wasting conditions like cachexia. In this review, we summarize recent developments in the biochemistry of ghrelin and GHS-R1a signaling. These include unravelling the enzymatic transformations that generate active ghrelin and the discovery of multiple proteins that interact with ghrelin and GHS-R1a to regulate signaling. Furthermore, we propose that harnessing these processes will lead to highly selective treatments to address obesity, diabetes, and other metabolism-linked disorders.
Identifiants
pubmed: 31636018
pii: S1043-2760(19)30203-6
doi: 10.1016/j.tem.2019.09.006
pmc: PMC7299083
mid: NIHMS1544074
pii:
doi:
Substances chimiques
Antimicrobial Cationic Peptides
0
Blood Proteins
0
Ghrelin
0
Receptors, Ghrelin
0
liver-expressed antimicrobial peptide 2, human
0
Acyltransferases
EC 2.3.-
MBOAT4 protein, human
EC 2.3.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-117Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM134102
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Références
Bioorg Med Chem Lett. 2015 Jul 15;25(14):2800-3
pubmed: 26009163
Structure. 2019 Mar 5;27(3):537-544.e4
pubmed: 30686667
J Biol Chem. 1998 May 29;273(22):14037-45
pubmed: 9593755
Mol Psychiatry. 2020 Feb;25(2):461-475
pubmed: 29728704
J Physiol. 2018 Nov;596(22):5415-5428
pubmed: 30199095
Mol Metab. 2015 Mar 21;4(6):437-60
pubmed: 26042199
J Mol Endocrinol. 2010 Feb;44(2):87-97
pubmed: 19625456
J Biol Chem. 2015 Feb 6;290(6):3293-307
pubmed: 25505265
Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6320-5
pubmed: 18443287
J Clin Invest. 2006 Mar;116(3):760-8
pubmed: 16511605
J Gastroenterol. 2011 Apr;46(4):469-78
pubmed: 21258824
Gen Comp Endocrinol. 2015 Dec 1;224:61-8
pubmed: 26073531
J Biol Chem. 2015 Jan 23;290(4):2235-43
pubmed: 25488661
Neuropharmacology. 2019 Jul 1;152:90-101
pubmed: 30582955
J Neurochem. 2018 Jan;144(1):58-67
pubmed: 29063591
Int J Obes (Lond). 2017 Sep;41(9):1413-1419
pubmed: 28529331
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2251-6
pubmed: 25646463
Neuron. 2010 Feb 11;65(3):320-7
pubmed: 20159446
Nature. 1999 Dec 9;402(6762):656-60
pubmed: 10604470
Methods Mol Biol. 2019;2009:227-241
pubmed: 31152408
Front Horm Res. 2014;42:163-74
pubmed: 24732934
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10255-E10264
pubmed: 30301804
Sci Signal. 2016 Apr 19;9(424):ra39
pubmed: 27095593
Nature. 2008 Aug 14;454(7206):846-51
pubmed: 18668043
Science. 2010 Dec 17;330(6011):1689-92
pubmed: 21097901
Cell Signal. 2011 May;23(5):837-48
pubmed: 21244856
Front Neurosci. 2013 Aug 30;7:148
pubmed: 24009547
FASEB J. 2019 Jan;33(1):518-531
pubmed: 30020830
Endocrinology. 2010 Oct;151(10):4765-75
pubmed: 20685872
Neuron. 2012 Jan 26;73(2):317-32
pubmed: 22284186
Biochemistry. 2017 Feb 21;56(7):919-931
pubmed: 28134508
Sci Rep. 2017 Mar 31;7:45541
pubmed: 28361877
Cell. 2015 Nov 19;163(5):1176-1190
pubmed: 26590421
Science. 1996 Aug 16;273(5277):974-7
pubmed: 8688086
Trends Biochem Sci. 2000 Mar;25(3):111-2
pubmed: 10694878
Cell Metab. 2018 Feb 6;27(2):461-469.e6
pubmed: 29233536
Peptides. 2011 Nov;32(11):2248-55
pubmed: 21619904
Cell Signal. 2007 May;19(5):1011-22
pubmed: 17229547
Endocrinology. 2007 May;148(5):2355-62
pubmed: 17289852
Genet Mol Biol. 2011 Apr;34(2):205-7
pubmed: 21734817
J Cell Physiol. 2007 Oct;213(1):187-200
pubmed: 17525997
J Neurosci. 2009 Nov 11;29(45):14057-65
pubmed: 19906954
N Engl J Med. 2013 Dec 26;369(26):2492-503
pubmed: 24206459
J Physiol Pharmacol. 2015 Aug;66(4):493-503
pubmed: 26348074
Eur J Med Chem. 2016 Nov 10;123:822-833
pubmed: 27541265
Bioorg Chem. 2015 Oct;62:64-73
pubmed: 26246082
Br J Pharmacol. 2004 Nov;143(5):520-3
pubmed: 15381634
Dev Cell. 2006 Dec;11(6):791-801
pubmed: 17141155
Endocr Dev. 2013;25:112-21
pubmed: 23652397
J Neuroendocrinol. 2019 Jul;31(7):e12677
pubmed: 30582239
J Mol Endocrinol. 2007 May;38(5):511-21
pubmed: 17496153
J Biol Chem. 2013 Jan 4;288(1):181-91
pubmed: 23161547
J Biol Chem. 2019 Sep 27;294(39):14166-14174
pubmed: 31413115
J Comp Neurol. 2006 Jan 20;494(3):528-48
pubmed: 16320257
J Clin Invest. 2019 Sep 3;129(9):3909-3923
pubmed: 31424424
Drug Des Devel Ther. 2018 Apr 18;12:873-885
pubmed: 29713145
Mol Cell Endocrinol. 2015 Sep 5;412:36-43
pubmed: 26001833
Bioorg Chem. 2018 Sep;79:98-106
pubmed: 29738973
FEBS J. 2019 Apr;286(7):1332-1345
pubmed: 30666806
Nat Commun. 2017 Sep 28;8(1):713
pubmed: 28959025
Chem Biol Interact. 2016 Nov 25;259(Pt B):271-275
pubmed: 26915976
Biochemistry. 2015 Feb 3;54(4):1100-10
pubmed: 25562443
Mol Endocrinol. 2007 Dec;21(12):3100-12
pubmed: 17717076
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10750-5
pubmed: 18669668
Mol Endocrinol. 1996 Jan;10(1):57-61
pubmed: 8838145
Endocrinology. 2016 Oct;157(10):3946-3957
pubmed: 27490185
Sci Rep. 2019 Feb 12;9(1):1841
pubmed: 30755699
J Biol Chem. 2005 Jul 1;280(26):25196-201
pubmed: 15899896
Mol Cell Endocrinol. 2013 Jan 30;365(2):303-8
pubmed: 23178796
ACS Chem Neurosci. 2015 Jul 15;6(7):1186-97
pubmed: 25727097
J Gen Physiol. 2015 Sep;146(3):205-19
pubmed: 26283199
Endocrinology. 2018 Feb 1;159(2):1021-1034
pubmed: 29300858
FASEB J. 2013 Dec;27(12):5112-21
pubmed: 23982145
Endocrine. 2016 Jun;52(3):609-17
pubmed: 26792793
eNeuro. 2015 Apr 24;2(2):
pubmed: 26464979
Nature. 2018 Oct;562(7726):286-290
pubmed: 30283133
SLAS Discov. 2018 Feb;23(2):154-163
pubmed: 28846466
Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10699-702
pubmed: 21928452
Pharmacol Rev. 2012 Oct;64(4):972-1003
pubmed: 22966038
Mol Membr Biol. 2016 Sep - Dec;33(6-8):111-124
pubmed: 29143554
Mol Neurobiol. 2019 Jun;56(6):4120-4134
pubmed: 30276663
Biochim Biophys Acta Mol Basis Dis. 2017 Oct;1863(10 Pt A):2462-2467
pubmed: 28499989
Anal Biochem. 2013 Jun 1;437(1):68-76
pubmed: 23453974
Nature. 2000 Oct 19;407(6806):908-13
pubmed: 11057670
Endocrinology. 2004 Nov;145(11):4997-5005
pubmed: 15256494
Vitam Horm. 2012;88:229-52
pubmed: 22391306
J Med Chem. 2000 Nov 16;43(23):4370-6
pubmed: 11087562
Neuroscience. 2011 Feb 3;174:50-63
pubmed: 21035522
Chem Biol Interact. 2015 Mar 5;229:1-8
pubmed: 25637688
Physiol Behav. 2016 Sep 1;163:88-96
pubmed: 27129673
Sci Transl Med. 2019 Aug 14;11(505):
pubmed: 31413143
Cell. 2008 Feb 8;132(3):387-96
pubmed: 18267071
Nature. 2001 Jan 11;409(6817):194-8
pubmed: 11196643
J Biol Chem. 2013 Nov 8;288(45):32211-28
pubmed: 24045953
J Med Chem. 2019 Jan 24;62(2):965-973
pubmed: 30543423
Neuroendocrinology. 2005;81(5):339-49
pubmed: 16210868
Neurosci Biobehav Rev. 2016 Jul;66:33-53
pubmed: 27136126