Chronic Energy Restriction Is Associated with Impaired Follicular Development and Hepatic Bile Acid Remodeling in Mice.
- 1Henan Provincial Engineering Research Center for Animal Germplasm Resources Exploration and Innovative Utilization, College of Biology and Food, Shangqiu Normal University, Shangqiu 476000, China.
- 2State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
Abstract
Chronic energy restriction (ER) can impair female reproductive function, but the peripheral metabolic mechanisms by which sustained energy deficiency disrupts follicular development remain poorly understood. This study aimed to determine whether hepatic bile acid (BA) remodeling contributes to the link between systemic energy availability and ovarian dysfunction. A chronic ER mouse model was established by reducing energy intake by 50% for 44 days. Multi-omics approaches, including hepatic transcriptomics, untargeted metabolomics, and targeted BA metabolomics, were integrated with ovarian functional analyses. ER significantly reduced ovarian weight, impaired follicular development, and decreased circulating concentrations of reproductive hormones. Hepatic transcriptomic and metabolomic analyses revealed extensive metabolic remodeling, with marked enrichment of BA-related pathways and increased expression of CYP7A1, suggesting increased hepatic BA synthetic capacity. Targeted BA profiling demonstrated elevated hepatic and circulating BA levels, including increased concentrations of several farnesoid X receptor (FXR)-activating BAs. Furthermore, ovarian FXR expression was increased, accompanied by decreased expression of key steroidogenic regulators, including SRB1, StAR, CYP11A1, and HSD3B1, consistent with reduced ovarian steroidogenic activity. These findings suggest that altered BA metabolism and increased ovarian FXR expression may contribute to reproductive dysfunction under chronic ER.
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BibTeX
@article{zhu2026chronic,
title = {{Chronic Energy Restriction Is Associated with Impaired Follicular Development and Hepatic Bile Acid Remodeling in Mice.}},
author = {Wenjun Zhu and Jiahao Li and Xiaochan Cheng and Hengyu Zhang and Li Li and Hengxi Wei and Shouquan Zhang},
journal = {Animals : an open access journal from MDPI},
year = {2026},
month = sep,
doi = {10.3390/ani16193025},
url = {https://europepmc.org/article/MED/42882994},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chronic Energy Restriction Is Associated with Impaired Follicular Development and Hepatic Bile Acid Remodeling in Mice.
AU - Wenjun Zhu
AU - Jiahao Li
AU - Xiaochan Cheng
AU - Hengyu Zhang
AU - Li Li
AU - Hengxi Wei
AU - Shouquan Zhang
PY - 2026
DA - 2026/09/25
JO - Animals : an open access journal from MDPI
DO - 10.3390/ani16193025
UR - https://europepmc.org/article/MED/42882994
AB - Chronic energy restriction (ER) can impair female reproductive function, but the peripheral metabolic mechanisms by which sustained energy deficiency disrupts follicular development remain poorly understood. This study aimed to determine whether hepatic bile acid (BA) remodeling contributes to the link between systemic energy availability and ovarian dysfunction. A chronic ER mouse model was established by reducing energy intake by 50% for 44 days. Multi-omics approaches, including hepatic transcriptomics, untargeted metabolomics, and targeted BA metabolomics, were integrated with ovarian functional analyses. ER significantly reduced ovarian weight, impaired follicular development, and decreased circulating concentrations of reproductive hormones. Hepatic transcriptomic and metabolomic analyses revealed extensive metabolic remodeling, with marked enrichment of BA-related pathways and increased expression of CYP7A1, suggesting increased hepatic BA synthetic capacity. Targeted BA profiling demonstrated elevated hepatic and circulating BA levels, including increased concentrations of several farnesoid X receptor (FXR)-activating BAs. Furthermore, ovarian FXR expression was increased, accompanied by decreased expression of key steroidogenic regulators, including SRB1, StAR, CYP11A1, and HSD3B1, consistent with reduced ovarian steroidogenic activity. These findings suggest that altered BA metabolism and increased ovarian FXR expression may contribute to reproductive dysfunction under chronic ER.
SN - 2076-2615
ER -