title: 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.
authors.affiliation: Section of Behavioral Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bellisario
authors.affiliation: Section of Behavioral Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Panetta
authors.affiliation: Max Planck Institute of Psychiatry, Department Stress Neurobiology and Neurogenetics, Munich, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Balsevich
authors.affiliation: Max Planck Institute of Psychiatry, Department Stress Neurobiology and Neurogenetics, Munich, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Baumann
authors.affiliation: UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: June
authors.initials: J
authors.lastname: Noble
authors.affiliation: Section of Behavioral Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Raggi
authors.affiliation: Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, Roslin, Edinburgh, Scotland, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Nathan
authors.affiliation: Section of Behavioral Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Berry
authors.affiliation: UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Seckl
authors.affiliation: Max Planck Institute of Psychiatry, Department Stress Neurobiology and Neurogenetics, Munich, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Megan
authors.initials: M
authors.lastname: Holmes
authors.affiliation: Section of Behavioral Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. Electronic address: francesca.cirulli@iss.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cirulli
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001923:Brain Chemistry / Q000187:drug effects; D002190:Cannibalism / Q000523:psychology; D003345:Corticosterone / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D002149:Energy Intake; D005260:Female; D005333:Fetus / Q000378:metabolism; D005938:Glucocorticoids / Q000502:physiology*; D020738:Leptin / Q000378:metabolism; D008425:Maternal Behavior; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology
chemical_list: D005938:Glucocorticoids; D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003345:Corticosterone
keywords: Animal models; Anxiety; High-fat diet; Maternal behavior; Pregnancy; Stress