A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene.
Animal
Humans
LEP
LEPR
Phenotype
Journal
Molecular and cellular pediatrics
ISSN: 2194-7791
Titre abrégé: Mol Cell Pediatr
Pays: Germany
ID NLM: 101660689
Informations de publication
Date de publication:
26 Aug 2021
26 Aug 2021
Historique:
received:
25
05
2021
accepted:
19
07
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
28
8
2021
Statut:
epublish
Résumé
Leptin (LEP) and leptin receptor (LEPR) play a major role in energy homeostasis, metabolism, and reproductive function. While effects of biallelic likely pathogenic variants (-/-) on the phenotype are well characterized, effects of mono-allelic likely pathogenic variants (wt/-) in the LEP and LEPR gene on the phenotype compared to wild-type homozygosity (wt/wt) have not been systematically investigated. We identified in our systematic review 44 animal studies (15 on Lep, 29 on Lepr) and 39 studies in humans reporting on 130 mono-allelic likely pathogenic variant carriers with 20 distinct LEP variants and 108 heterozygous mono-allelic likely pathogenic variant carriers with 35 distinct LEPR variants. We found indications for a higher weight status in carriers of mono-allelic likely pathogenic variant in the leptin and in the leptin receptor gene compared to wt/wt, in both animal and human studies. In addition, animal studies showed higher body fat percentage in Lep and Lepr wt/- vs wt/wt. Animal studies provided indications for lower leptin levels in Lep wt/- vs. wt/wt and indications for higher leptin levels in Lepr wt/- vs wt/wt. Data on leptin levels in human studies was limited. Evidence for an impaired metabolism in mono-allelic likely pathogenic variants of the leptin and in leptin receptor gene was not conclusive (animal and human studies). Mono-allelic likely pathogenic variants in the leptin and in leptin receptor gene have phenotypic effects disposing to increased body weight and fat accumulation.
Identifiants
pubmed: 34448070
doi: 10.1186/s40348-021-00119-7
pii: 10.1186/s40348-021-00119-7
pmc: PMC8390564
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
10Subventions
Organisme : German Ministry of Education and Research (BMBF)
ID : FKZ 01GI1120A and 01GI1127
Organisme : Competence Network Obesity
ID : FKZ 01GI1401
Organisme : Hertha-Nathorff-Programm of the Medical Faculty of the University of Ulm
ID : LSSH1000.07
Organisme : Hertha-Nathorff-Programm of the Medical Faculty of the University of Ulm
ID : KSKI, 002.1
Organisme : German Research Association
ID : FI1700/7-1, Heisenberg Professorship
Informations de copyright
© 2021. The Author(s).
Références
Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R975-81
pubmed: 16339386
Endocrinology. 2015 Jan;156(1):360-6
pubmed: 25353183
Nat Med. 2018 May;24(5):551-555
pubmed: 29736023
Carcinogenesis. 2004 May;25(5):821-5
pubmed: 14729596
Am J Physiol Renal Physiol. 2007 Nov;293(5):F1512-7
pubmed: 17881464
Mol Genet Metab. 2009 Aug;97(4):305-8
pubmed: 19427251
J Nutr. 1996 Oct;126(10):2487-93
pubmed: 8857509
Obes Facts. 2016;9(3):158-73
pubmed: 27241181
Diabetologia. 1981 May;20(5):573-7
pubmed: 7026332
Int J Obes Relat Metab Disord. 1997 Apr;21(4):321-6
pubmed: 9130031
Science. 1979 Feb 16;203(4381):663-5
pubmed: 760211
Endocrine. 2014 Apr;45(3):401-8
pubmed: 23824601
Mol Cell Pediatr. 2014 Dec;1(1):3
pubmed: 26567097
Endocrinology. 2001 Jul;142(7):2888-97
pubmed: 11416008
Pediatr Res. 1989 Feb;25(2):173-9
pubmed: 2919132
Nature. 1995 Oct 12;377(6549):530-2
pubmed: 7566151
Cell. 2019 Apr 18;177(3):597-607.e9
pubmed: 31002796
Hepatology. 2013 Feb;57(2):543-54
pubmed: 22941940
Am J Physiol. 1998 Apr;274(4):R985-90
pubmed: 9575960
Diabetes. 2002 Jun;51(6):1980-5
pubmed: 12031989
Int J Pediatr Obes. 2011 Oct;6(5-6):419-27
pubmed: 21854111
Endocr J. 2009;56(8):997-1008
pubmed: 19706988
Endocrinology. 2008 Jan;149(1):174-84
pubmed: 17932216
Am J Hum Genet. 1962 Dec;14:353-62
pubmed: 13937884
Am J Physiol. 1995 Jan;268(1 Pt 1):E15-20
pubmed: 7840172
Acta Paediatr Suppl. 2006 Apr;450:76-85
pubmed: 16817681
J Appl Physiol (1985). 2008 Jul;105(1):249-59
pubmed: 18467551
Obes Res Clin Pract. 2009 Mar;3(1):1-52
pubmed: 24345539
Biochem Biophys Res Commun. 1997 Nov 17;240(2):492-5
pubmed: 9388507
HPB (Oxford). 2006;8(5):386-92
pubmed: 18333092
Science. 1995 Jul 28;269(5223):543-6
pubmed: 7624777
Hum Mutat. 2016 Jun;37(6):564-9
pubmed: 26931183
Am J Physiol. 1969 Nov;217(5):1298-304
pubmed: 5346292
J Clin Endocrinol Metab. 2001 Jul;86(7):3284-91
pubmed: 11443202
Science. 1966 Sep 2;153(3740):1127-8
pubmed: 5918576
Obes Rev. 2018 Nov;19(11):1525-1543
pubmed: 30261552
EBioMedicine. 2018 Oct;36:390-400
pubmed: 30266296
Cell. 1996 Feb 9;84(3):491-5
pubmed: 8608603
Sci Rep. 2017 Mar 24;7:45130
pubmed: 28338021
Biomed Res Int. 2014;2014:912052
pubmed: 24707501
J Clin Endocrinol Metab. 2010 Jun;95(6):2836-40
pubmed: 20382689
Biol Res. 2016 Apr 13;49:23
pubmed: 27075752
J Med Genet. 1994 Feb;31(2):89-98
pubmed: 8182727
Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E362-9
pubmed: 21558549
Eur J Endocrinol. 2011 Apr;164(4):521-7
pubmed: 21296922
J Clin Res Pediatr Endocrinol. 2017 Dec 08;10(3):274-278
pubmed: 29217499
Eur J Med Genet. 2018 Aug;61(8):465-467
pubmed: 29545012
Biochem Biophys Res Commun. 1968 Dec 30;33(6):883-7
pubmed: 5750852
Nature. 1996 Jul 18;382(6588):250-2
pubmed: 8717038
Lab Anim Res. 2015 Mar;31(1):1-6
pubmed: 25806077
Biochim Biophys Acta. 1982 Mar 12;710(3):290-6
pubmed: 7074117
J Biol Chem. 1975 Jun 25;250(12):4702-7
pubmed: 167002
Cell Metab. 2017 Jul 5;26(1):24-26
pubmed: 28648981
Horm Res Paediatr. 2016;85(6):412-20
pubmed: 26925581
J Exp Med. 1999 Aug 16;190(4):497-507
pubmed: 10449521
J Clin Endocrinol Metab. 1998 Sep;83(9):3239-42
pubmed: 9745435
N Engl J Med. 2003 Mar 20;348(12):1096-103
pubmed: 12646666
Am J Physiol Endocrinol Metab. 2008 May;294(5):E939-51
pubmed: 18349116
Pediatr Res. 2003 Mar;53(3):411-8
pubmed: 12595588
Reprod Sci. 2011 Apr;18(4):342-52
pubmed: 21266665
Diabetologia. 2018 Nov;61(11):2422-2432
pubmed: 30094465
J Endocrinol. 2014 Oct;223(1):T1-8
pubmed: 25121999
Nat Genet. 1998 Mar;18(3):213-5
pubmed: 9500540
J Bone Miner Res. 2003 Sep;18(9):1605-11
pubmed: 12968669
Am J Physiol. 1998 Oct;275(4):R1106-9
pubmed: 9756540
Mol Genet Metab. 2011 Apr;102(4):461-4
pubmed: 21306929
PLoS One. 2008 Aug 29;3(8):e3098
pubmed: 18769731
J Clin Endocrinol Metab. 2015 Sep;100(9):3227-30
pubmed: 26186301
Exp Anim. 2005 Jan;54(1):13-20
pubmed: 15725677
Biol Reprod. 2014 Feb 20;90(2):33
pubmed: 24389871
J Nutr. 1994 Aug;124(8):1230-7
pubmed: 7914918
Clin Genet. 2014 Oct;86(4):391-3
pubmed: 24304187
Cell Mol Life Sci. 2015 Feb;72(3):629-644
pubmed: 25098352
Diabetes. 2012 Feb;61(2):383-90
pubmed: 22210313
Mol Genet Metab. 2012 May;106(1):121-6
pubmed: 22463805
Am J Physiol. 1997 Jan;272(1 Pt 1):E100-6
pubmed: 9038858
Am J Physiol. 1985 Feb;248(2 Pt 1):E188-93
pubmed: 3881986
J Gastrointest Surg. 2004 Dec;8(8):971-81; discussion 981-2
pubmed: 15585384
Horm Metab Res. 2000 Jul;32(7):269-72
pubmed: 10965932
Mol Cell Pediatr. 2017 Nov 3;4(1):10
pubmed: 29101506
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7806-9
pubmed: 1881916
Am J Physiol. 1999 May;276(5):E836-42
pubmed: 10329976
Obes Res. 1999 May;7(3):293-8
pubmed: 10348501
Clin Sci (Lond). 2016 Jun 1;130(12):943-86
pubmed: 27154742
J Endocrinol. 2014 Oct;223(1):T9-23
pubmed: 25063754
Nature. 1994 Dec 1;372(6505):425-32
pubmed: 7984236
Anat Rec (Hoboken). 2015 Dec;298(12):2018-29
pubmed: 26370912
J Clin Endocrinol Metab. 1998 May;83(5):1407-13
pubmed: 9589630
J Neurosci. 2001 Dec 15;21(24):RC186
pubmed: 11734601
J Clin Endocrinol Metab. 2015 May;100(5):E757-66
pubmed: 25751111
Nature. 1997 Jun 26;387(6636):903-8
pubmed: 9202122
Diabetes. 2000 Aug;49(8):1347-52
pubmed: 10923636
Eur J Endocrinol. 2017 Mar;176(3):315-322
pubmed: 28007844
Nat Med. 1997 Feb;3(2):238-40
pubmed: 9018247
Am J Physiol. 1984 May;246(5 Pt 1):E391-6
pubmed: 6720944
Endocr Rev. 2016 Aug;37(4):347-71
pubmed: 27187081
Horm Metab Res. 2002 Nov-Dec;34(11-12):686-90
pubmed: 12660883
Neurology. 2014 Jan 14;82(2):139-48
pubmed: 24336230
Clin Genet. 1984 May;25(5):381-415
pubmed: 6373070
Nature. 1996 Feb 15;379(6566):632-5
pubmed: 8628397
J Cell Biochem. 2005 Sep 1;96(1):89-96
pubmed: 16052473
Mol Genet Metab. 2017 May;121(1):51-56
pubmed: 28377240
J Hered. 1950 Dec;41(12):317-8
pubmed: 14824537
J Clin Endocrinol Metab. 1999 Oct;84(10):3686-95
pubmed: 10523015
Diabetologia. 1973 Aug;9(4):294-8
pubmed: 4767369
Nat Genet. 1997 Jul;16(3):218-20
pubmed: 9207782
Diabetes. 2008 Sep;57(9):2511-8
pubmed: 18559663
Nature. 2001 Nov 1;414(6859):34-5
pubmed: 11689931
J Dairy Sci. 2008 Jul;91(7):2893-900
pubmed: 18565947
Obesity (Silver Spring). 2015 Aug;23(8):1687-95
pubmed: 26179253
N Engl J Med. 2007 Jan 18;356(3):237-47
pubmed: 17229951
Obes Res. 2001 Oct;9(10):627-30
pubmed: 11595779
Gut. 2002 Jun;50(6):797-802
pubmed: 12010881
J Endocrinol. 2014 Oct;223(1):T63-70
pubmed: 25232148
J Cell Biochem. 2017 Dec;118(12):4762-4771
pubmed: 28523647
Metabolism. 2021 Mar;116:154438
pubmed: 33221380
Nature. 1998 Mar 26;392(6674):398-401
pubmed: 9537324
Physiol Genomics. 2010 Mar 3;41(1):9-20
pubmed: 19996157
Genes (Basel). 2019 May 07;10(5):
pubmed: 31067764
Obes Rev. 2007 Jul;8(4):293-306
pubmed: 17578380
Endocrinology. 2015 Oct;156(10):3777-90
pubmed: 26196541
Am J Physiol. 1999 Apr;276(4):E762-5
pubmed: 10198314
J Endocr Soc. 2018 Sep 17;3(1):27-41
pubmed: 30560226
BMC Med Genet. 2018 Aug 2;19(1):135
pubmed: 30068297
J Pediatr Hematol Oncol. 2003 Oct;25(10):791-6
pubmed: 14528102
Obesity (Silver Spring). 2014 Apr;22(4):1112-7
pubmed: 24319006
J Gastrointest Surg. 2003 Nov;7(7):857-62; discussion 863
pubmed: 14592658
Science. 1995 Jul 28;269(5223):546-9
pubmed: 7624778
J Clin Res Pediatr Endocrinol. 2019 Apr 17;11(4):341-349
pubmed: 30991789
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2601-2612
pubmed: 29726959