A Maternal Low-protein Diet during Gestation Induces Hepatic Autophagy-related Gene Expression in a Sex-specific Manner in Sprague-Dawley Rats

Mingzhu Cai, Jie Zhang, Hong Chen, Yuan-Xiang Pan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalBritish Journal of Nutrition
DOIs
StateAccepted/In press - 2021

Keywords

  • Autophagy
  • Genes
  • Maternal protein deficiency
  • Sex difference
  • Transcription factor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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