Perinatal Exposure to Western Diet Programs Autonomic Dysfunction in the Male Offspring
Open accessAbstract
Although the deleterious influence of protein deficiency on fetal programming is well documented, the impact of a Western diet on epigenetic mechanisms is less clear. We hypothesized that high-fat high-sucrose diet (HFHSD) consumption during pregnancy leads to epigenetic modifications within the progeny's compensatory renin-angiotensin system (RAS), affecting autonomic and metabolic functions. Dams were fed HFHSD (45% fat and 30% sucrose) or regular chow (RD) from mating until weaning of the pups (~7 weeks). Offspring from both groups were then maintained on chow and studied in adulthood (3-7 months). Offspring from HFHSD-exposed dams (OH) exhibited no difference in body weight or fasting blood glucose compared to controls (OR). In 3-month-old offspring, DNA methylation was significantly lower for the ACE2 gene (P < 0.05) in the brainstem, kidney and cecum. Moreover, ACE2 activity in the hypothalamus was increased at 7 months (OH: 91 ± 1 vs. OR: 74 ± 4 AFU/mg/min, P < 0.05). Although baseline blood pressure was not different between groups, vagal tone in OH was significantly impaired compared to OR. At the same time, OH offspring had a 1.7-fold increase in AT 1a receptor expression and a 1.3-fold increase in ADAM17 mRNA. DOCA-salt treatment further revealed and exacerbated hypertensive response in the OH progeny (OH: 130 ± 6 vs. OR: 108 ± 3 mmHg, P < 0.05). Taken together, our data suggest that perinatal exposure to HFHSD resulted in epigenetic modifications of the compensatory brain RAS, potentially affecting plasticity of neuronal networks leading to autonomic dysfunction in the male offspring.
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In mice, perinatal exposure to a high-fat, high-sucrose diet epigenetically primes the central renin-angiotensin system, leading to hypertension, potentially owing to limited plasticity of the autonomic system.
“For example, in mice, perinatal exposure to a high-fat, high-sucrose diet epi-genetically primed the central renin-angiotensin system leading to hypertension, potentially owing to limited plasticity of the autonomic system202.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [202]
Epigenetic inheritance may explain much of the heritability of hypertension.
“Epigenetic inheritance may explain much of the heritability of hypertension202.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [202]
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The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753 · see citing works
- Authors
- Mukerjee, S., Zhu, Y., Zsombok, A., Mauvais-Jarvis, F., Zhao, J., & Lazartigues, E.
- Affiliations
- Louisiana State University Health Sciences Center New Orleans (US)
- University of Florida (US)
- Tulane University (US)
- Louisiana State University (US)
- Corresponding author
- Lazartigues, Eric
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2017-05-06
- Volume
- 38
- Issue
- 1
- Pages
- 233-242
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC5673595
- OpenAlex
- W2611950821
- Cited by
- 18
- References
- 54
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- American Heart Association (12EIA8030004)
- National Center for Research Resources (RR018766)
- National Institute of General Medical Sciences (GM103514, GM106392)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- Western diet, perinatal programming, fetal programming, DNA methylation, ACE2, renin-angiotensin system, autonomic dysfunction, vagal tone, AT1a receptor, ADAM17, DOCA-salt hypertension, hypothalamus, brainstem, cecum, male offspring
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Blood Glucose, Blood Pressure, Body Weight, Brain, Female, Male, Mice, Inbred C57BL, Pregnancy, Prenatal Exposure Delayed Effects, Renin-Angiotensin System, DNA Methylation, Epigenesis, Genetic, Mice, Diet, Western
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