• Interaction of uteroplacental...

*Result*: Interaction of uteroplacental insufficiency and postnatal Western diet on the hepatic transcriptome in young adult female and male Guinea pigs.

Title:
Interaction of uteroplacental insufficiency and postnatal Western diet on the hepatic transcriptome in young adult female and male Guinea pigs.
Authors:
Sarr O; Department of Physiology and Pharmacology, Western University, London, ON, Canada., Thompson JA; Department of Physiology and Pharmacology, Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada. Electronic address: Jennifer.thompson2@ucalgary.ca., Lam NLH; Department of Physiology and Pharmacology, Western University, London, ON, Canada. Electronic address: nlam55@uwo.ca., Kiser PK; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada. Electronic address: pkiser@uwo.ca., Regnault TRH; Department of Physiology and Pharmacology, Western University, London, ON, Canada; Department of Obstetrics and Gynaecology, Western University, London, ON, Canada; Children's Health Research Institute, London, ON, Canada. Electronic address: tim.regnault@uwo.ca.
Source:
Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2026 Feb; Vol. 1872 (2), pp. 168054. Date of Electronic Publication: 2025 Oct 31.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-260X (Electronic) Linking ISSN: 09254439 NLM ISO Abbreviation: Biochim Biophys Acta Mol Basis Dis Subsets: MEDLINE
Imprint Name(s):
Original Publication: Amsterdam : Elsevier
MeSH Terms:
Liver*/metabolism , Liver*/pathology , Transcriptome* , Placental Insufficiency*/metabolism , Placental Insufficiency*/genetics , Placental Insufficiency*/pathology , Diet, Western*/adverse effects , Fetal Growth Retardation*/metabolism , Fetal Growth Retardation*/genetics , Fetal Growth Retardation*/pathology , Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/pathology , Non-alcoholic Fatty Liver Disease*/genetics , Non-alcoholic Fatty Liver Disease*/etiology, Animals ; Female ; Male ; Guinea Pigs ; Pregnancy
Contributed Indexing:
Keywords: Guinea pig; Liver; Low birth weight; Transcriptome; Western diet
Entry Date(s):
Date Created: 20251101 Date Completed: 20251116 Latest Revision: 20251116
Update Code:
20260130
DOI:
10.1016/j.bbadis.2025.168054
PMID:
41175852
Database:
MEDLINE

*Further Information*

*Epidemiological and animal studies highlight an adverse in utero environment, often associated with low birth weight (LBW) and intrauterine growth restriction (IUGR), and postnatal intake of energy-dense foods, interact in the development of nonalcoholic fatty liver disease (NAFLD) in offspring. While these associations are emerging, understanding the specific contributions of LBW/IUGR and energy-dense food such as Western diet (WD) to the hepatic transcriptome and development of NAFLD is lacking. This study used a guinea pig model of uteroplacental insufficiency (UPI) to induce LBW/IUGR. It applied microarray-based expression profiling with epigenetic marker analysis to explore mechanisms by which UPI may predisposes WD-fed young adult offspring to NAFLD. At postnatal day 150, male and female WD offspring exhibited lean NAFLD, regardless of birth weight. WD consumption led to downregulation of the steroid biosynthesis, upregulation of ECM-receptor interaction, cell cycle, lysosome, and AGE-RAGE signaling pathways in both sexes. Additionally, genes in the p53 signaling pathway were upregulated in WD males, while the PPAR signaling pathway was upregulated in WD females, independent of birth weight. MicroRNA (miR)-target gene interactions and RTqPCR analyses revealed that miR-26b-5p in males and miR-29-3p in females were linked to these pathway changes. The combination of LBW and WD caused changes in hepatic adrenergic and calcium signaling in females and NF-kappa beta signaling in males. This study shows that although LBW and WD each uniquely and jointly affect the hepatic transcriptome, WD alone appears to be a significant environment underlying NAFLD in young adult female and male guinea pigs.
(Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)*

*Declaration of competing interest The authors declare that they have no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported.*