In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring
Open accessAbstract
The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.
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Exposure to prepregnancy maternal obesity impairs the activity of factors involved in mitochondrial dynamics in the offspring.
“exposure to prepregnancy maternal obesity impairs the activity of factors involved in mitochondrial dynamics in the offspring (Borengasser et al., 2014).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Borengasser et al., 2014
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- Authors
- Borengasser, S. J., Faske, J., Kang, P., Blackburn, M. L., Badger, T. M., & Shankar, K.
- Affiliations
- Arkansas Children's Nutrition Center (US)
- Corresponding author
- Shankar, Kartik
- Venue
- Physiological Genomics
- Publisher
- American Physiological Society
- Published
- 2014-12-01
- Volume
- 46
- Issue
- 23
- Pages
- 841-850
- ISSN
- 1094-8341 (ISSN-L)
- 1531-2267
- PMC
- PMC4254938
- OpenAlex
- W2000234289
- Cited by
- 76
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 15 · 2019: 3 · 2018: 9 · 2017: 13 · 2016: 5 · 2015: 8
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Genomics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007446, R01DK084225)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- maternal obesity, pre-pregnancy obesity, prenatal exposure, mitochondrial dynamics, mitochondrial fusion, mitochondrial fission, placenta, offspring, metabolic programming, OPA1, mitofusins, PARL, NRF1, PGC-1α, estrogen-related receptor alpha, energy expenditure, fat utilization, liver, skeletal muscle
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Animal Nutritional Physiological Phenomena, Animals, Newborn, Calorimetry, Indirect, Female, Liver, Male, Membrane Proteins, Obesity, Placenta, Pregnancy, Time Factors, Transcription Factors, Weaning, Rats, Sprague-Dawley, Muscle, Skeletal, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, GTP Phosphohydrolases, Mitochondrial Proteins, Prenatal Nutritional Physiological Phenomena, Metalloproteases, Diet, High-Fat, Mitochondrial Dynamics
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