Inter- and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic.
arsenic
diabetes
environmental health
epigenetic inheritance
metabolism
obesity
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
19
07
2020
revised:
26
11
2020
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
16
11
2021
Statut:
epublish
Résumé
The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross-generational effects of iAs in an exclusive male-lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6-phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male-lineage iAs exposure show increased adiposity, especially on a high-calorie diet. These findings have unveiled sex- and generation-specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene-environment interactions.
Identifiants
pubmed: 33854880
doi: 10.1002/advs.202002715
pii: ADVS2356
pmc: PMC8025034
doi:
Substances chimiques
Arsenic
N712M78A8G
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
2002715Subventions
Organisme : NICHD NIH HHS
ID : U54 HD083092
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA126752
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111436
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114356
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153320
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006348
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103555
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027544
Pays : United States
Informations de copyright
© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Nature. 2010 Oct 21;467(7318):963-6
pubmed: 20962845
Environ Health Perspect. 2016 Mar;124(3):336-43
pubmed: 26295903
Clin Epigenetics. 2015 Apr 29;7:55
pubmed: 25984247
Arch Toxicol. 2018 Jun;92(6):1925-1937
pubmed: 29721587
Endocrinology. 2006 Jun;147(6 Suppl):S50-5
pubmed: 16690801
Nat Metab. 2019 Jan;1(1):34-46
pubmed: 32694818
Curr Environ Health Rep. 2018 Mar;5(1):134-144
pubmed: 29411302
Environ Health Perspect. 2017 Dec 20;125(12):127004
pubmed: 29373862
Environ Int. 2018 Oct;119:250-263
pubmed: 29982128
Food Chem Toxicol. 2017 Sep;107(Pt A):406-417
pubmed: 28709971
Environ Health Perspect. 2016 Feb;124(2):201-9
pubmed: 26151952
Met Ions Biol Med. 2008;10:1-7
pubmed: 20467584
In Vitro. 1981 Oct;17(10):913-25
pubmed: 6273298
J Pediatr (Rio J). 2007 Nov-Dec;83(6):494-504
pubmed: 18074050
J Proteome Res. 2019 Mar 1;18(3):970-981
pubmed: 30545218
Clin Sci (Lond). 1983 Jan;64(1):7-18
pubmed: 6337008
Obesity (Silver Spring). 2015 Apr;23(4):862-9
pubmed: 25755147
Environ Health Perspect. 2014 Mar;122(3):284-91
pubmed: 24413286
PLoS One. 2015 Jul 31;10(7):e0134333
pubmed: 26230509
Environ Health Perspect. 2011 Aug;119(8):1104-9
pubmed: 21592922
Science. 2016 Jan 22;351(6271):397-400
pubmed: 26721680
Hum Reprod Update. 2015 Mar-Apr;21(2):194-208
pubmed: 25416302
Curr Pharmacol Rep. 2019 Dec;5(6):491-504
pubmed: 31929964
Trends Endocrinol Metab. 2020 Jul;31(7):478-494
pubmed: 32521235
Environ Health. 2019 Feb 28;18(1):18
pubmed: 30819207
Br Med Bull. 2001;60:5-20
pubmed: 11809615
Environ Health. 2017 May 30;16(1):50
pubmed: 28558807
Biomed Res Int. 2019 Oct 15;2019:4978018
pubmed: 31737665
Nat Genet. 2016 May;48(5):497-9
pubmed: 26974008
Hum Genomics. 2015 Jul 28;9:17
pubmed: 26216216
Arch Biochem Biophys. 1998 Mar 15;351(2):279-85
pubmed: 9514661
Toxicol Appl Pharmacol. 2005 Aug 7;206(2):169-75
pubmed: 15967205
Exp Clin Endocrinol Diabetes. 2011 Nov;119(10):613-7
pubmed: 22068553
Epigenet Insights. 2018 Oct 14;11:2516865718803641
pubmed: 30443644
Cell. 2010 Dec 23;143(7):1084-96
pubmed: 21183072
Adv Sci (Weinh). 2021 Feb 18;8(7):2002715
pubmed: 33854880
Toxicol Appl Pharmacol. 2018 Jan 1;338:124-133
pubmed: 29175454
Toxicol Appl Pharmacol. 2019 Aug 15;377:114605
pubmed: 31170414
Nature. 2019 Jul;571(7766):489-499
pubmed: 31341302
Curr Top Dev Biol. 2018;127:119-147
pubmed: 29433735
Curr Diab Rep. 2019 Nov 22;19(12):147
pubmed: 31758285
Cell Metab. 2016 Apr 12;23(4):735-43
pubmed: 26908462
Toxicol Sci. 2011 Oct;123(2):305-32
pubmed: 21750349
Gut Pathog. 2013 Apr 30;5(1):10
pubmed: 23631345
Clin Epigenetics. 2020 May 12;12(1):65
pubmed: 32398147
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cell. 2014 Mar 27;157(1):95-109
pubmed: 24679529
Syst Biol Reprod Med. 2018 Dec;64(6):469-483
pubmed: 29873257
Environ Int. 2018 Mar;112:183-197
pubmed: 29275244
Epigenomics. 2010 Feb;2(1):87-104
pubmed: 20514360
Toxicol Appl Pharmacol. 2018 Nov 1;358:43-55
pubmed: 30213730
Environ Int. 2018 Sep;118:97-105
pubmed: 29859944
Annu Rev Public Health. 2018 Apr 1;39:309-333
pubmed: 29328878
Environ Health Perspect. 2012 Jun;120(6):779-89
pubmed: 22296744
Food Chem Toxicol. 2017 Feb;100:207-216
pubmed: 28017702
Annu Rev Genomics Hum Genet. 2008;9:233-57
pubmed: 18767965
BMC Gastroenterol. 2015 Aug 11;15:100
pubmed: 26261039
Am J Physiol. 1998 Jun;274(6):G1087-93
pubmed: 9696709
Sci Rep. 2018 Aug 22;8(1):12627
pubmed: 30135504
Chemosphere. 2019 Dec;236:124325
pubmed: 31326754
Nat Rev Genet. 2018 Feb;19(2):81-92
pubmed: 29033456
Nat Rev Endocrinol. 2019 Aug;15(8):489-498
pubmed: 31235802
Environ Health Perspect. 2016 Feb;124(2):170-5
pubmed: 26115410
PLoS One. 2014 Jan 08;9(1):e84689
pubmed: 24416266
Environ Health Perspect. 2013 Mar;121(3):295-302
pubmed: 23458756
Nat Rev Genet. 2017 Sep;18(9):517-534
pubmed: 28555658
Environ Health Perspect. 2016 Aug;124(8):1253-60
pubmed: 26771251