Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids’ signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice
Abstract
Maternal diet during pregnancy can impact maternal behavior as well as the intrauterine environment, playing a critical role in programming offspring's physiology. In a preliminary study, we found a strong association between high-fat diet (HFD) during pregnancy and increased cannibalistic episodes and dams' mortality during late pregnancy and parturition. Based upon these data, we hypothesized that HFD during pregnancy could negatively affect neuroendocrine and metabolic regulations occurring during the final stages of pregnancy, thereby disrupting maternal behavior. To test this hypothesis, female C57BL/6J mice were fed HFD or control diet for 11 weeks until three days before the expected delivery date. Basal corticosterone plasma levels and brain levels of c-Fos were measured both before and after delivery, in addition to leptin levels in the adipose tissue. Dam's emotional behavior and social anxiety, in addition to locomotor activity were assessed before parturition. Data show that HFD led to aberrant maternal behavior, dams being characterized by behaviors related to aggression toward an unfamiliar social stimulus in the social avoidance test, in addition to decreased locomotor activity. Neural activity in HFD dams was reduced in the olfactory bulbs, a crucial brain region for social and olfactory recognition hence essential for maternal behavior. Furthermore, HFD feeding resulted in increased circulating levels of maternal corticosterone and decreased levels of leptin. In addition, the activity of the protective 11β-dehydrogenase-2 (11β-HSD-2) barrier in the placenta was decreased together with 11β-dehydrogenase-1 (11β-HSD-1) gene expression. Overall, these data suggest that HFD acts as a stressful challenge during pregnancy, impairing the neuroendocrine system and the neural activity of brain regions involved in the processing of relevant olfactory stimuli, with negative consequences on maternal physiology and behavior.
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Maternal stress and early life stress are associated with decreases in birth weight and litter size, and increases in maternal cannibalism of pups.
“Along with hypermethylation of stress-related genes, maternal stress and ELS are associated with decreases in birth weight35, 36 and litter size37, and increases in maternal cannibalism of pups38, 39.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [39]
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- Authors
- Bellisario, V., Panetta, P., Balsevich, G., Baumann, V., Noble, J., Raggi, C., Nathan, O., Berry, A., Seckl, J., Schmidt, M., Holmes, M., & Cirulli, F.
- Affiliations
- Istituto Superiore di Sanità (IT)
- Max Planck Institute of Psychiatry (DE)
- The Queen's Medical Research Institute (GB)
- University of Edinburgh (GB)
- Corresponding author
- Cirulli, Francesca
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 60
- Pages
- 138-150
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W1880247794
- Cited by
- 88
- References
- 58
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 6 · 2020: 3 · 2019: 12 · 2018: 7 · 2017: 14 · 2016: 8 · 2015: 2
- FWCI
- 16.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Fondazione Cariplo
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- maternal high-fat diet, pregnancy, maternal behavior, glucocorticoids, corticosterone, leptin, olfactory bulb, social anxiety, aggression, locomotor activity, c-fos, placenta, neuroendocrine regulation, maternal stress, C57BL/6J mice
- MeSH terms
- Animals, Brain, Brain Chemistry, Energy Intake, Cannibalism, Corticosterone, Female, Fetus, Glucocorticoids, Maternal Behavior, Mice, Inbred C57BL, Motor Activity, Pregnancy, Stress, Psychological, Signal Transduction, Proto-Oncogene Proteins c-fos, Leptin, 11-beta-Hydroxysteroid Dehydrogenase Type 1, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Mice, Diet, High-Fat
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