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

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

Author Pantaleao, Lucas Carminatti Google Scholar
Murata, Gilson Google Scholar
Teixeira, Caio Jordao Google Scholar
Payolla, Tanyara Baliani Google Scholar
Santos-Silva, Junia Carolina Google Scholar
Duque-Guimaraes, Daniella Esteves Google Scholar
Sodre, Frhancielly S. Google Scholar
Lellis-Santos, Camilo Autor UNIFESP Google Scholar
Vieira, Juliana Camargo Google Scholar
de Souza, Dailson Nogueira Google Scholar
Gomes, Patricia Rodrigues Google Scholar
Rodrigues, Sandra Campos Google Scholar
Anhe, Gabriel Forato Google Scholar
Bordin, Silvana Google Scholar
Abstract We 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.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
National Counsel of Technological and Scientific Development (CNPq)
Coordination for the Improvement of Higher Level or Education Personnel (CAPES)
Date 2017
Published in Scientific Reports. London, v. 7, p. -, 2017.
ISSN 2045-2322 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Origin http://dx.doi.org/10.1038/s41598-017-10642-1
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000408997700066
URI https://repositorio.unifesp.br/handle/11600/57377

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