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Parental high-fat/high-sugar diets and their lasting impact on brain development in offspring: a longitudinal mouse
Gail Lee1,2,3, Karina Wilk4,5, Cheryl Chong6
1Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada. gailc.lee@alumni.utoronto.ca.
Insights
Maternal high-fat diets alter offspring brain development, causing lasting structural changes even after a healthy diet is introduced. These neuroanatomical alterations may increase the risk for neurodevelopmental disorders (NDDs).
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Maternal metabolic conditions and diet impact offspring neurodevelopment and neurodevelopmental disorder (NDD) risk.
- The temporal sequence of neuroanatomical changes due to maternal diet is not well understood.
Purpose of the Study:
- To investigate the longitudinal effects of parental high-fat/high-sugar diets on offspring brain development and structure.
- To identify specific brain regions and developmental time points affected by maternal dietary interventions.
Main Methods:
- Utilized a mouse model exposing parents to high-fat or high-fat/high-sugar diets during gestation and lactation.
- Employed longitudinal magnetic resonance imaging (MRI) to track offspring brain structural changes from early development through adulthood.
- Assessed brain region volumes and changes over time, including after a diet switch at weaning.
Main Results:
- Parental high-fat/high-sugar diets induced significant offspring brain structural changes.
- Observed distinct temporal patterns: early-onset changes (some transient, some persistent), and pubertal-emerging changes.
- Brain alterations persisted into adulthood, even with a healthy diet post-weaning, affecting regions like the cingulate cortex, hippocampus, and orbitofrontal cortex.
Conclusions:
- Maternal diet profoundly impacts offspring neurodevelopment, leading to persistent, long-term neuroanatomical changes.
- These diet-induced brain alterations may contribute to the risk of neurodevelopmental disorders (NDDs).
- The study provides a valuable model for understanding diet-related NDD risk and exploring preventative strategies.
Abstract:
Maternal diet and metabolic conditions, such as obesity and diabetes, are associated with consequences for offspring brain health, including effects on behaviour and an increased risk for neurodevelopmental disorders (NDDs). The extent and sequence of neuroanatomical changes to offspring brain development produced by dietary conditions have not yet been reported. In this study, we used a mouse model of parental high-fat or high-fat/high-sugar diet consumption to examine its effects on offspring brain development using longitudinal magnetic resonance imaging. We demonstrated that exposure to these parental diets through gestation and lactation resulted in offspring brain structure changes. Different temporal patterns of change were observed: some structures exhibited volume differences already at postnatal day 3; some of these early appearing changes diminished early in development while others were still present in adulthood; other structure changes were found to emerge later in the pubertal period. Brain changes in adulthood were present despite switching to a healthy diet at weaning. Brain regions impacted included the cingulate cortex, subregions of the hippocampus, and the orbitofrontal cortex, regions previously reported as affected in human NDD populations, with functional roles in reward processing and social cognition, memory, and decision making, respectively. Affected cortical regions, including the cingulate and orbitofrontal cortex, were found to be increased in volume relative to the whole brain, while affected subcortical regions were largely decreased in volume. Our data provide new insights into the long-term neuroanatomical impact of parental diets and how those diets may impact NDD risk. Future studies could use this model to evaluate preventative or ameliorative measures.
