MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 04 2021
26 04 2021
Historique:
received:
05
01
2021
accepted:
07
04
2021
entrez:
27
4
2021
pubmed:
28
4
2021
medline:
11
11
2021
Statut:
epublish
Résumé
Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.
Identifiants
pubmed: 33903707
doi: 10.1038/s41598-021-88518-8
pii: 10.1038/s41598-021-88518-8
pmc: PMC8076304
doi:
Substances chimiques
MicroRNAs
0
mirnlet7 microRNA, mouse
0
AMP-Activated Protein Kinases
EC 2.7.11.31
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
8980Subventions
Organisme : NICHD NIH HHS
ID : R01 HD099813
Pays : United States
Références
J Nutr Biochem. 2016 Aug;34:30-41
pubmed: 27180121
J Lipid Res. 2017 Feb;58(2):443-454
pubmed: 27913585
Stem Cells. 2013 Aug;31(8):1563-73
pubmed: 23666760
Neuroscience. 2018 Feb 10;371:1-15
pubmed: 29203230
Cell Rep. 2019 Jan 2;26(1):192-208.e6
pubmed: 30605676
Biochem J. 2015 Dec 1;472(2):147-56
pubmed: 26378151
Biochimie. 2020 Jan;168:198-209
pubmed: 31715215
Trends Cell Biol. 2012 Sep;22(9):474-82
pubmed: 22784697
Int J Mol Sci. 2013 Apr 17;14(4):8437-55
pubmed: 23594995
Elife. 2015 Oct 07;4:e09431
pubmed: 26445246
Oncogene. 2017 Apr 27;36(17):2345-2354
pubmed: 27775072
Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21075-80
pubmed: 22160727
Nat Protoc. 2013 Jun;8(6):1149-54
pubmed: 23702831
Placenta. 2011 Feb;32(2):121-7
pubmed: 21144584
Med Hypotheses. 2012 Feb;78(2):262-9
pubmed: 22129484
Hypertens Res. 2010 Jan;33(1):22-8
pubmed: 19911004
Metabolism. 2014 May;63(5):682-92
pubmed: 24636055
Nutr Metab (Lond). 2017 Feb 20;14:16
pubmed: 28239403
Cell. 2011 Sep 30;147(1):81-94
pubmed: 21962509
Hepatol Commun. 2020 Aug 09;4(10):1392-1403
pubmed: 33024911
Semin Cell Dev Biol. 2015 Jul;43:85-95
pubmed: 26135290
J Dev Orig Health Dis. 2020 Oct 07;:1-11
pubmed: 33023711
Curr Opin Lipidol. 2016 Apr;27(2):172-80
pubmed: 26906549
PLoS One. 2016 Aug 01;11(8):e0160184
pubmed: 27479001
Trends Endocrinol Metab. 2017 Aug;28(8):545-560
pubmed: 28647324
Am J Physiol Endocrinol Metab. 2016 Oct 1;311(4):E730-E740
pubmed: 27577854