A maternal low-protein diet during gestation induces hepatic autophagy-related gene expression in a sex-specific manner in Sprague-Dawley rats
Author(s)
Cai, Mingzhu
Zhang, Jie
Chen, Hong
Pan, Yuan-Xiang
Type
Journal Article
Abstract
This study investigates the mechanism by which maternal protein restriction induces hepatic autophagy-related gene expression in the offspring of rats. Pregnant Sprague-Dawley rats were fed either a control diet (C, 18% energy from protein) or a low-protein diet (LP, 8.5% energy from protein) during gestation, followed by the control diet during lactation and post-weaning. Liver tissue was collected from the offspring at postnatal day 38 and divided into four groups according to sex and maternal diet (F-C, F-LP, M-C, and M-LP) for further analysis. Autophagy-related mRNA and protein levels were determined by real-time PCR and Western blotting, respectively. In addition, chromatin immunoprecipitation (ChIP) was performed to investigate the interactions between transcription factors and autophagy-related genes. Protein levels of p-eIF2a and ATF4 were increased only in the female offspring born to dams fed the LP diet. Correlatively, the mRNA expression of hepatic autophagy-related genes including Map1lc3b, P62/Sqstm1, Becn1, Atg3, Atg7, and Atg10 was significantly greater in the F-LP group than in the F-C group. Furthermore, ChIP results showed greater ATF4 and C/EBP homology protein (CHOP) binding at the regions of a set of autophagy-related genes in the F-LP group than in the F-C group. Our data demonstrated that a maternal LP diet transcriptionally programmed hepatic autophagy-related gene expression only in female rat offspring. This transcriptional program involved the activation of the eIF2α/ATF4 pathway and intricate regulation by transcription factors ATF4 and CHOP.
Date Issued
2022-08-28
Date Acceptance
2021-09-01
Citation
British Journal of Nutrition, 2022, 128 (4), pp.592-603
ISSN
0007-1145
Publisher
Cambridge University Press (CUP)
Start Page
592
End Page
603
Journal / Book Title
British Journal of Nutrition
Volume
128
Issue
4
Copyright Statement
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/maternal-lowprotein-diet-during-gestation-induces-hepatic-autophagyrelated-gene-expression-in-a-sexspecific-manner-in-spraguedawley-rats/6AFE17B0F2D5F61748A7B2241448F010
Subjects
Science & Technology
Life Sciences & Biomedicine
Nutrition & Dietetics
Maternal protein deficiency
Genes
Autophagy
Transcription factor
Sex difference
ACID RESPONSE PATHWAY
LIPID-METABOLISM
SKELETAL-MUSCLE
PREGNANT RATS
RESTRICTION
BINDING
ENVIRONMENT
IMPACT
LIVER
LEADS
Autophagy
Genes
Maternal protein deficiency
Sex difference
Transcription factor
0702 Animal Production
0908 Food Sciences
1111 Nutrition and Dietetics
Nutrition & Dietetics
Publication Status
Published
Date Publish Online
2021-09-13