Maternal High-Fat Feeding Primes Steatohepatitis in Adult Mice Offspring, Involving Mitochondrial Dysfunction and Altered Lipogenesis Gene Expression
Open accessAbstract
UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring. CONCLUSION: Maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism and up-regulated hepatic lipogenesis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a mouse model, maternal obesity led to profound changes in offspring liver histology and physiology, including increased hepatic lipid content, decreased HDL cholesterol, increased fasting insulin, TNF-α, DNA oxidative damage markers, and hepatic protein oxidation.
“The results of this study highlight how maternal obesity led to profound changes in the offspring’s liver histology and physiology; histological analysis shows an increase in hepatic lipid content compared to control subjects. Plasma analysis showed a decrease in HDL cholesterol, an increase in fasting insulin, TNF-α and DNA oxidative damage markers and hepatic protein oxidation.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
Sexually dimorphic differences in body composition are already present at birth.
“at birth, fat mass accounts for approximately 15% of neonatal body weight, and sexually dimorphic differences in body composition are already present.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
Adipose tissue develops prenatally, with marked expansion during the third trimester of pregnancy; at birth, fat mass accounts for approximately 15% of neonatal body weight.
“Adipose tissue develops prenatally, with marked expansion during the third trimester of pregnancy; at birth, fat mass accounts for approximately 15% of neonatal body weight, and sexually dimorphic differences in body composition are already present.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
The distribution of adipose tissue depends on sex and environmental factors, such as exposure to maternal obesity in utero, which can modify its programming as it does for all other tissues.
“It is evident that the distribution of adipose tissue depends on sex and environmental factors, such as exposure to maternal obesity in utero, which can modify its programming as it does for all other tissues [80,81].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
Maternal obesity in mice led to variations in protein expression involved in oxidative stress homeostasis, including reduced NADPH oxidase and glutathione peroxidase, increased catalase, decreased lipogenesis and lipolysis proteins, and increased PPARγ.
“Also, variations in protein expression involved in oxidative stress homeostasis were found, including reduced expression of NADPH oxidase and glutathione peroxidase, an increase in catalase and a decrease in protein levels involved in lipogenesis and lipolysis; in particular, an increase in PPARγ expression was discovered.”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
Maternal obesity in mice led to mitochondrial damage with increased activity of complexes I and II and a significant reduction in cytochrome C expression.
“Regarding mitochondrial damage, there was an increase in the activity of complexes I and II and a significant reduction in cytochrome C expression [80,81].”
From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [81]
Cites
Mitochondrial dysfunction in Nash: causes, consequences and possible means to prevent it
Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B. (2006) · Mitochondrion · doi:10.1016/j.mito.2005.10.004 · Cited by 753 · see citing works
Taylor, P. D., McConnell, J., Khan, I. Y., Holemans, K., Lawrence, K. M., Asare-Anane, H., Persaud, S. J., Jones, P. M., Petrie, L., Hanson, M. A., et al. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00355.2004 · Cited by 297 · see citing works
Self-citationMembrane-linked systems preventing superoxide formation
Skulachev, V. P. (1997) · Bioscience Reports · doi:10.1023/a:1027344914565 · Cited by 162 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?
Hanson, M. A., & Gluckman, P. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00029.2013 · Cited by 1,188 · see citing works
Self-citationMetabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101 · see citing works
Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes
Maniam, J., Antoniadis, C., & Morris, M. J. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00073 · Cited by 295 · see citing works
Bouret, S., Levin, B. E., & Ozanne, S. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00007.2014 · Cited by 157 · see citing works
Mouralidarane, A., Soeda, J., Visconti-Pugmire, C., Samuelsson, A.-M., Pombo, J., Maragkoudaki, X., Butt, A., Saraswati, R., Novelli, M., Fusai, G., et al. (2013) · Hepatology · doi:10.1002/hep.26248 · Cited by 145 · see citing works
Self-citationAlfaradhi, M. Z., Fernandez-Twinn, D. S., Martin-Gronert, M. S., Musial, B., Fowden, A., & Ozanne, S. E. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00049.2014 · Cited by 136 · see citing works
Borengasser, S. J., Faske, J., Kang, P., Blackburn, M. L., Badger, T. M., & Shankar, K. (2014) · Physiological Genomics · doi:10.1152/physiolgenomics.00059.2014 · Cited by 76 · see citing works
Ding, Y., Li, J., Liu, S., Zhang, L., Xiao, H., Li, J., Chen, H., Petersen, R. B., Huang, K., & Zheng, L. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.98 · Cited by 76 · see citing works
Authors, & Collaborators: (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-2388 · Cited by 30 · see citing works
Schiera, G., Macajone, G., Volpes, S., Greco, L., Di Liegro, C. M., Serio, G., Caradonna, F., & Naselli, F. (2026) · Cells · doi:10.3390/cells15040366 · Cited by 8 · see citing works
- Authors
- Bruce, K. D., Cagampang, F. R., Argenton, M., Zhang, J., Ethirajan, P. L., Burdge, G. C., Bateman, A. C., Clough, G. F., Poston, L., Hanson, M. A., McConnell, J. M., & Byrne, C. D.
- Affiliations
- Southampton General Hospital (GB)
- King's College London (GB)
- University Hospital Coventry (GB)
- Corresponding author
- Bruce, Kimberley D.
- ORCID
- Venue
- Hepatology
- Published
- 2009-12
- Volume
- 50
- Issue
- 6
- Pages
- 1796-1808
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2037841634
- Cited by
- 449
- References
- 3
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 14 · 2023: 22 · 2022: 29 · 2021: 21 · 2020: 25 · 2019: 32 · 2018: 34 · 2017: 27 · 2016: 37 · 2015: 34 · 2014: 38 · 2013: 33 · 2012: 23
- FWCI
- 18.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/D001633/1)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, maternal high-fat diet, developmental programming, hepatic mitochondrial dysfunction, electron transport chain, oxidative stress, liver inflammation
- MeSH terms
- Animals, Dietary Fats, Disease Models, Animal, Electron Transport, Fatty Liver, Female, Gene Expression Regulation, Mice, Inbred C57BL, Mitochondria, Liver, Pregnancy, Polymerase Chain Reaction, Oxidative Stress, Hyaluronan Receptors, Maternal Nutritional Physiological Phenomena, Lipogenesis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
