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Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers

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cam.issuedOnline2021-10-12
dc.contributor.authorCampos, CV
dc.contributor.authorTeixeira, CJ
dc.contributor.authorPayolla, TB
dc.contributor.authorCrisma, AR
dc.contributor.authorMurata, GM
dc.contributor.authorAmaral, AG
dc.contributor.authorPantaleão, LC
dc.contributor.authorSodré, FS
dc.contributor.authorOnari, MM
dc.contributor.authorAlmeida, LDS
dc.contributor.authorPereira, GA
dc.contributor.authorGuimarães, DSSF
dc.contributor.authorSilveira, LR
dc.contributor.authorAnhê, GF
dc.contributor.authorBordin, S
dc.contributor.orcidTeixeira, CJ [0000-0002-4951-1130]
dc.contributor.orcidCrisma, AR [0000-0002-5810-9717]
dc.contributor.orcidPantaleão, LC [0000-0002-5626-8810]
dc.contributor.orcidGuimarães, DSSF [0000-0002-3890-2910]
dc.contributor.orcidBordin, S [0000-0002-0192-8869]
dc.date.accessioned2021-10-14T03:30:01Z
dc.date.available2021-10-14T03:30:01Z
dc.date.issued2021-10-12
dc.date.updated2021-10-14T03:30:00Z
dc.description.abstract<jats:p>In the present study we investigated the participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in the metabolic programming of newborn rats exposed in utero to dexamethasone (DEX). On the 21st day of life, fasted offspring born to DEX-treated mothers displayed increased conversion of pyruvate into glucose with simultaneous upregulation of PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). Increased oxidative phosphorylation, higher ATP/ADP ratio and mitochondrial biogenesis and lower pyruvate levels were also found in the progeny of DEX-treated mothers. On the other hand, the 21-day-old progeny of DEX-treated mothers had increased hepatic triglycerides (TAG) and lower CPT-1 activity when subjected to short-term fasting. At the mechanistic level, rats exposed in utero to DEX exhibited increased hepatic PGC-1α protein content with lower miR-29a-c expression. Increased PGC-1α content was concurrent with increased association to HNF-4α and NRF1 and reduced PPARα expression. The data presented herein reveal that changes in the transcription machinery in neonatal liver of rats born to DEX-treated mothers leads to an inflexible metabolic response to fasting. Such programming is hallmarked by increased oxidative phosphorylation of pyruvate with impaired FFA oxidation and hepatic TAG accumulation.</jats:p>
dc.identifier.doi10.17863/CAM.76845
dc.identifier.eissn2673-4389
dc.identifier.issn2673-4389
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329397
dc.languageen
dc.language.isoeng
dc.publisherMDPI AG
dc.publisher.urlhttp://dx.doi.org/10.3390/livers1040016
dc.subject3101 Biochemistry and Cell Biology
dc.subject32 Biomedical and Clinical Sciences
dc.subject31 Biological Sciences
dc.subjectDigestive Diseases
dc.subjectDiabetes
dc.subjectPediatric
dc.subjectPerinatal Period - Conditions Originating in Perinatal Period
dc.subjectLiver Disease
dc.titleChanges in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers
dc.typeArticle
dcterms.dateAccepted2021-10-09
prism.endingPage220
prism.issueIdentifier4
prism.publicationNameLivers
prism.startingPage201
prism.volume1
pubs.funder-project-idFundação de Amparo à Pesquisa do Estado de São Paulo (2013/07607-8, 2014/02977-4, 2016/22605-0, 2019/03196-0, 2020/06397-3, 2020/09717-9)
pubs.funder-project-idCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (001)
pubs.funder-project-idConselho Nacional de Desenvolvimento Científico e Tecnológico (PQ2)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/livers1040016

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