Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 2.32 MB
Add to list
  1. Search results
  2. Mitochondrial dysfunction characteris...

Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD

Anneleen Heldens (UGent) , Milton Boaheng Antwi (UGent) , Louis Onghena (UGent) , Tim Meese, Yannick Gansemans (UGent) , Joél Smet (UGent) , Ellen Dupont, Xavier Verhelst (UGent) , Sarah Raevens (UGent) , Hans Van Vlierberghe (UGent) , et al.
(2025) JHEP REPORTS. 7(6).
Author
Organization
Project
Abstract
Background & aims Although maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal Western diet (WD) on MASLD progression, and test drug candidates. Methods Female mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 24 days, 10 and 16 weeks (n=5-11 per group). Additionally, offspring from dams with hepatic insulin receptor knock-out were evaluated (n=9-12 per group). Serum fibroblast growth factor 21 (FGF21) and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) were measured in adolescents with MASLD ± a history of maternal obesity. The therapeutic efficacy of FGF21, semaglutide and an amylin analogue was assessed from 8 to 16 weeks of age (n=8-12 per group). Results Starting from weaning age, maternal WD feeding aggravated body weight gain, insulin resistance, steatosis and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Isolated maternal hepatic insulin resistance partially recapitulated offspring inflammation and fibrosis. Notably, OXPHOS was also downregulated in a transcriptomic dataset of maternal WD feeding in non-human primates. Serum FGF21 and MOTS-c correlated with MASLD severity and maternal obesity in adolescents. Particularly FGF21 treatment ameliorated steatohepatitis and mitochondrial function. Conclusions Maternal WD aggravates MASLD in male offspring starting from weaning age, with mitochondrial dysfunction contributing to disease severity. This was reversed by FGF21 agonism.
Keywords
MASH, NAFLD, FGF21, Oxidative phosphorylation, NONALCOHOLIC FATTY LIVER, WEIGHT-LOSS, DISEASE, STEATOHEPATITIS, LIPOGENESIS, PROGRAMS, RISK

Downloads

  • Download
    publisher version.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 2.32 MB

Citation

Please use this url to cite or link to this publication:

MLA
Heldens, Anneleen, et al. “Mitochondrial Dysfunction Characterises the Multigenerational Effects of Maternal Obesity on MASLD.” JHEP REPORTS, vol. 7, no. 6, 2025, doi:10.1016/j.jhepr.2025.101404.
APA
Heldens, A., Antwi, M. B., Onghena, L., Meese, T., Gansemans, Y., Smet, J., … Lefere, S. (2025). Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD. JHEP REPORTS, 7(6). https://doi.org/10.1016/j.jhepr.2025.101404
Chicago author-date
Heldens, Anneleen, Milton Boaheng Antwi, Louis Onghena, Tim Meese, Yannick Gansemans, Joél Smet, Ellen Dupont, et al. 2025. “Mitochondrial Dysfunction Characterises the Multigenerational Effects of Maternal Obesity on MASLD.” JHEP REPORTS 7 (6). https://doi.org/10.1016/j.jhepr.2025.101404.
Chicago author-date (all authors)
Heldens, Anneleen, Milton Boaheng Antwi, Louis Onghena, Tim Meese, Yannick Gansemans, Joél Smet, Ellen Dupont, Xavier Verhelst, Sarah Raevens, Hans Van Vlierberghe, Arnaud Vanlander, Filip Van Nieuwerburgh, Lindsey Devisscher, Ruth De Bruyne, Anja Geerts, and Sander Lefere. 2025. “Mitochondrial Dysfunction Characterises the Multigenerational Effects of Maternal Obesity on MASLD.” JHEP REPORTS 7 (6). doi:10.1016/j.jhepr.2025.101404.
Vancouver
1.
Heldens A, Antwi MB, Onghena L, Meese T, Gansemans Y, Smet J, et al. Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD. JHEP REPORTS. 2025;7(6).
IEEE
[1]
A. Heldens et al., “Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD,” JHEP REPORTS, vol. 7, no. 6, 2025.
@article{01JVS5QBWWFG5A9060TGF0GRVQ,
  abstract     = {{Background & aims
Although maternal obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the pathogenesis remains unclear. We aimed to evaluate the effect and mechanisms of multigenerational maternal Western diet (WD) on MASLD progression, and test drug candidates.

Methods
Female mice were fed WD from 8 weeks before breeding initiation with a normal chow (NC)-fed male, throughout pregnancy and lactation. Male offspring were weaned onto NC or WD and assessed at the age of 24 days, 10 and 16 weeks (n=5-11 per group). Additionally, offspring from dams with hepatic insulin receptor knock-out were evaluated (n=9-12 per group). Serum fibroblast growth factor 21 (FGF21) and mitochondrial open reading frame of 12S rRNA-c (MOTS-c) were measured in adolescents with MASLD ± a history of maternal obesity. The therapeutic efficacy of FGF21, semaglutide and an amylin analogue was assessed from 8 to 16 weeks of age (n=8-12 per group).

Results
Starting from weaning age, maternal WD feeding aggravated body weight gain, insulin resistance, steatosis and inflammation. Fibrosis was only observed in offspring exposed to maternal WD. Mechanistically, the latter exhibited reduced OXPHOS activity. Isolated maternal hepatic insulin resistance partially recapitulated offspring inflammation and fibrosis. Notably, OXPHOS was also downregulated in a transcriptomic dataset of maternal WD feeding in non-human primates. Serum FGF21 and MOTS-c correlated with MASLD severity and maternal obesity in adolescents. Particularly FGF21 treatment ameliorated steatohepatitis and mitochondrial function.

Conclusions
Maternal WD aggravates MASLD in male offspring starting from weaning age, with mitochondrial dysfunction contributing to disease severity. This was reversed by FGF21 agonism.}},
  articleno    = {{101404}},
  author       = {{Heldens, Anneleen and Antwi, Milton Boaheng and Onghena, Louis and Meese, Tim and Gansemans, Yannick and Smet, Joél and Dupont, Ellen and Verhelst, Xavier and Raevens, Sarah and Van Vlierberghe, Hans and Vanlander, Arnaud and Van Nieuwerburgh, Filip and Devisscher, Lindsey and De Bruyne, Ruth and Geerts, Anja and Lefere, Sander}},
  issn         = {{2589-5559}},
  journal      = {{JHEP REPORTS}},
  keywords     = {{MASH,NAFLD,FGF21,Oxidative phosphorylation,NONALCOHOLIC FATTY LIVER,WEIGHT-LOSS,DISEASE,STEATOHEPATITIS,LIPOGENESIS,PROGRAMS,RISK}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{13}},
  title        = {{Mitochondrial dysfunction characterises the multigenerational effects of maternal obesity on MASLD}},
  url          = {{http://doi.org/10.1016/j.jhepr.2025.101404}},
  volume       = {{7}},
  year         = {{2025}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: