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Sci Rep 2017 Sep 04;71:10367. doi: 10.1038/s41598-017-10642-1.
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Prolonged fasting elicits increased hepatic triglyceride accumulation in rats born to dexamethasone-treated mothers.

Pantaleão LC , Murata G , Teixeira CJ , Payolla TB , Santos-Silva JC , Duque-Guimaraes DE , Sodré FS , Lellis-Santos C , Vieira JC , de Souza DN , Gomes PR , Rodrigues SC , Anhe GF , Bordin S .

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.

PubMed ID: 28871187
PMC ID: PMC5583317
Article link: Sci Rep

Species referenced: Echinodermata
Genes referenced: fasn LOC575101 LOC578064 LOC580672 LOC583082 LOC586683 LOC587157 LOC587800 LOC590297 LOC590371 LOC752072 LOC752532 mttp pklr rpl37a sgpl1 slc2a1 yy1

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References [+] :
Agarwal, Predicting effective microRNA target sites in mammalian mRNAs. 2015, Pubmed