Prolonged fasting elicits increased hepatic triglyceride accumulation in rats born to dexamethasone-treated mothers

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dc.citation.volume7
dc.contributor.authorPantaleao, Lucas Carminatti
dc.contributor.authorMurata, Gilson
dc.contributor.authorTeixeira, Caio Jordao
dc.contributor.authorPayolla, Tanyara Baliani
dc.contributor.authorSantos-Silva, Junia Carolina
dc.contributor.authorDuque-Guimaraes, Daniella Esteves
dc.contributor.authorSodre, Frhancielly S.
dc.contributor.authorLellis-Santos, Camilo [UNIFESP]
dc.contributor.authorVieira, Juliana Camargo
dc.contributor.authorde Souza, Dailson Nogueira
dc.contributor.authorGomes, Patricia Rodrigues
dc.contributor.authorRodrigues, Sandra Campos
dc.contributor.authorAnhe, Gabriel Forato
dc.contributor.authorBordin, Silvana
dc.coverageLondon
dc.date.accessioned2020-08-04T13:40:13Z
dc.date.available2020-08-04T13:40:13Z
dc.date.issued2017
dc.description.abstractWe investigated the effect of dexamethasone during the last week of pregnancy on glucose and lipid metabolism in male offspring. Twelve-week old offspring were evaluated after fasting for 12-hours (physiological) and 60-hours (prolonged). Physiological fasting resulted in glucose intolerance, decreased glucose clearance after pyruvate load and increased PEPCK expression in rats born to dexamethasone-treated mothers (DEX). Prolonged fasting resulted in increased glucose tolerance and increased glucose clearance after pyruvate load in DEX. These modulations were accompanied by accumulation of hepatic triglycerides (TG). Sixty-hour fasted DEX also showed increased citrate synthase (CS) activity, ATP citrate lyase (ACLY) content, and pyruvate kinase 2 (pkm2), glucose transporter 1 (slc2a1) and lactate dehydrogenase-a (ldha) expressions. Hepatic AKT2 was increased in 60-hour fasted DEX, in parallel with reduced miRNAs targeting the AKT2 gene. Altogether, we show that metabolic programming by prenatal dexamethasone is characterized by an unexpected hepatic TG accumulation during prolonged fasting. The underlying mechanism may depend on increased hepatic glycolytic flux due to increased pkm2 expression and consequent conversion of pyruvate to non-esterified fatty acid synthesis due to increased CS activity and ACLY levels. Upregulation of AKT2 due to reduced miRNAs may serve as a permanent mechanism leading to increased pkm2 expression.en
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Diadema, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Diadema, Brazil
dc.description.provenanceMade available in DSpace on 2020-08-04T13:40:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2017. Added 1 bitstream(s) on 2020-08-04T14:42:06Z : No. of bitstreams: 1 WOS000408997700066.pdf: 1525636 bytes, checksum: bf61205fcc1b00538728c6f41023191b (MD5)en
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipNational Counsel of Technological and Scientific Development (CNPq)
dc.description.sponsorshipCoordination for the Improvement of Higher Level or Education Personnel (CAPES)
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dc.identifierhttp://dx.doi.org/10.1038/s41598-017-10642-1
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/s41598-017-10642-1
dc.identifier.fileWOS000408997700066.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57377
dc.identifier.wosWOS:000408997700066
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsAcesso aberto
dc.titleProlonged fasting elicits increased hepatic triglyceride accumulation in rats born to dexamethasone-treated mothersen
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