A maternal low-protein diet during gestation induces hepatic autophagy gene expression only in the female offspring Sprague-Dawley rats

Maternal protein restriction is associated with inducting of gene expression programs. Multiple stress-induced genes are known to be activated through eIF2α phosphorylation and induction of activating transcription factor 4 (ATF4), which also potentially play a role in autophagy related-genes expression. The present study investigates the mechanisms by which maternal protein restriction induce autophagy related-gene expression in the liver of offspring rats. In this study, pregnant Sprague-Dawley rats were fed either a control diet (18% energy from protein) or a low-protein diet (8.5% energy from protein) during gestation period followed by the control diet during lactation. Offspring consumed the same control post-weaning diet from postnatal day 21. Liver tissue was collected at postnatal day 38 from the offspring. The maternal low-protein diet significantly induced mRNA expression of the stress- response genes including Atf3 and Chop in liver of female offspring, but not in male. Moreover, mRNA expression of hepatic autophagy gene including LC3b, P62/SQSTM1, Beclin1, Atg3, Atg7, Atg5, and Atg10 was increased significantly only in the female offspring by gestational low-protein diet. The induction of gene expression was consistent with the activated eIF2a/ATF4 pathway in female offspring. Furthermore, we found the maternal low-protein diet induces ATF4 and C/EBP homology protein (CHOP) binding at the regions of specific autophagy-related genes in the liver of female offspring through differential cooperative regulation. Overall, our data demonstrated that hepatic autophagy gene expression could be induced by a maternal LP diet only in the female rat offspring. This transcriptional program involves in activated p- eIF2α/ATF4 pathway and cooperative regulation of transcription factors ATF4 and CHOP.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2018

Author dc:creator

• Cai, Mingzhu

Contributors dc:contributor

• Pan, Yuan-Xiang

• Maternal low-protein diet, Autophagy, Gene, Transcription factor

Statement dc:rights

• Copyright 2018 Mingzhu Cai

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/101749

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/101749