Disentangling Fat and Sugar in the Western Diet: Parental Consumption of a High-Fat Diet Alters Offspring Brain Development

Background: Maternal consumption of the Western diet is a precursor for metabolic conditions such as obesity and is associated with increased offspring risk for neurodevelopmental disorders (NDDs). It is not clear which component (i.e., high-fat or high-sugar) of the Western diet contributes to changes in offspring neurodevelopment. We used a mouse model of parental consumption of five different diets containing varying levels of fat and sugar to examine and compare their effects on offspring brain structure. Methods: Male and female offspring (avg n = 15/sex/diet) were assessed for differences in body weight and developmental milestone achievement, and their brains were imaged at postnatal day (P) 65 using magnetic resonance imaging to compare brain structure. Results: Offspring of the high-fat-only and combined high-fat/high-sugar diet groups showed delayed righting reflex success and heavier weight at weaning. Brain structure differences were also observed in early adulthood (P65), with the pattern of change induced by high-fat/high-sugar diets similar to that observed in some autism mouse models. Conclusions: Parental high-fat-only and combined high-fat/high-sugar diets altered offspring brain structure, but the high-sugar-only diet did not. High fat consumption is likely a key driver of the observed offspring brain changes and is a modifiable risk factor for NDDs.