Summary: Maternal stress during pregnancy increases the likelihood that female offspring will develop binge-eating-like behavior, but a methyl-balanced diet during adolescence can prevent this predisposition, new mouse research shows.
Source: Cell Press.
Stress alters eating behavior, and new preclinical research in mice indicates that the cause may involve biological programming as well as psychology. A study published May 30 in Cell Metabolism reports that activating a specific prenatal stress circuit in pregnant mice leads female offspring to carry epigenetic changes in the hypothalamus and to develop binge-eating-like behavior when later exposed to stressful, food-restricted conditions. Importantly, placing those offspring on a diet balanced in methyl-donating nutrients such as vitamin B12 and folate during adolescence prevented the binge-eating phenotype.
Epidemiological studies have long linked early-life trauma and stress with an increased risk of binge eating and related disorders, but the biological mechanisms have been difficult to define. To isolate one pathway, researchers genetically engineered mice so they could selectively activate the corticotropin-releasing factor (CRF) neuroendocrine circuit that drives stress-hormone release. In humans, elevated CRF activity is associated with anxiety, appetite suppression, inflammation, and long-term health effects.
During the late gestation period (the mouse equivalent of the human third trimester), investigators triggered CRF activity in pregnant dams using a low-intervention method designed to avoid additional handling stress. The brief, targeted activation produced prenatal stress (PNS) while minimizing other stressors that could confound results.
Analysis of the offspring revealed that female pups from CRF-activated mothers carried epigenetic methylation changes in hypothalamic tissue, including altered regulation of microRNA and downstream melanocortin pathways. However, these epigenetic marks did not automatically produce binge-eating behavior. The predisposition manifested only when the adolescent offspring were placed on a restricted feeding schedule that limited access to a highly palatable diet to 2-hour windows three times per week. Under that limited-access condition, the mice were free to consume as much as they wanted during the windows, prompting episodes of rapid, excessive intake that resemble binge eating.
Remarkably, all ten female offspring exposed to both prenatal CRF activation and the limited-access feeding schedule showed a binge-eating-like phenotype, while genetically similar female littermates that were not challenged with the restrictive feeding schedule did not develop the behavior. This pattern suggests gestational programming creates a vulnerability that is revealed only under later-life stress or challenge.
Because methyl groups used for epigenetic marking are derived from nutrients such as vitamin B12 and folate, the authors tested whether dietary levels of methyl-donating vitamins could modify the outcome. When predisposed offspring were fed an adolescent diet balanced for methyl donors, the binge-eating-like behavior did not emerge despite prenatal stress and subsequent limited food access. These results point to a non-invasive preventive strategy—dietary balancing of methyl-donor nutrients during critical developmental windows—that mitigates the epigenetically programmed risk in this mouse model.
The investigators caution this is a preclinical study in animals. The exact dietary composition that constitutes a methyl-balanced diet for humans, and whether such a dietary approach would influence human eating disorders, remain unknown and require clinical testing. As the senior author notes, the methyl balance found to be protective here may not directly translate to people.
This work highlights that eating disorders can have a strong biological component. Prenatal environmental factors can induce long-lasting epigenetic changes and alter brain circuits in ways that increase vulnerability to psychiatric and metabolic conditions later in life. Minimizing stress during pregnancy and understanding how nutrition interacts with epigenetic programming are important directions for future research.
About this neuroscience research article
Funding: The research received support from several sources, including the European Research Council, the Israel Science Foundation, the Israeli Ministry of Health, the German Federal Ministry of Education and Research (BMBF), and multiple philanthropic foundations and research centers.
Source summary: Diana Crow, Cell Press. The original peer-reviewed study is titled “A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype” by Mariana Schroeder et al., published online May 30, 2017 in Cell Metabolism.
Abstract
Title: A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype
Highlights
- Prenatal stress predisposes female offspring to binge-eating-like behavior.
- Binge eating results from hypothalamic programming at multiple epigenetic levels.
- A methyl-balanced diet during adolescence can prevent the predisposition from being triggered.
Summary: Binge eating is characterized by episodes of excessive food consumption within a short time and is more prevalent in females, often associated with early-life adversity. This study demonstrates that late-gestation activation of the corticotropin-releasing factor (CRF) system predisposes female mouse offspring to binge-eating-like behavior. The predisposition coincides with hypomethylation of hypothalamic microRNA (miR-1a) and dysregulation of the melanocortin system via Pax7/Pax3 pathways. Crucially, exposing the offspring to a methyl-balanced diet during adolescence prevented these molecular changes and the behavioral outcome. The findings indicate that prenatal programming alone does not inevitably produce binge eating; rather, a later-life challenge reveals the vulnerability. The results provide experimental evidence linking prenatal stress, long-term epigenetic abnormalities, and risk for binge-eating behavior in females, and they suggest a potential, non-invasive dietary prevention strategy in this animal model.