Maternal high-fat diet and autism-relevant behavioural domains: insights from social and anxiety-like behaviours in rodent models.

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition involving interactions between genetic and environmental factors. Among environmental exposures, maternal nutrition has received increasing attention. This narrative review critically discusses preclinical evidence on maternal high-fat diet (HFD) exposure and autism-relevant behavioural domains in rodent offspring, focusing on social and anxiety-like behaviours and their underlying neurobiological mechanisms. Maternal HFD exposure was associated with alterations in sociability, social novelty, direct social interaction, aggression, and anxiety-like behaviour. These outcomes varied according to diet and control-diet composition, exposure window, maternal metabolic phenotype, offspring sex and age, species and strain, and behavioural paradigm. Despite significant evidence, the methodological heterogeneity between studies limits the generalisability of the findings and points to the need for standardisation of experimental protocols and further investigation of dimorphic differences and long-term impacts. Additionally, this review highlights the importance of considering contextual factors, such as variations in dietary composition and environmental conditions, which may modulate behavioural and neurochemical outcomes. Furthermore, the integration of interdisciplinary approaches and use of more refined models may improve our understanding of the underlying mechanisms. This review contributes to advancing knowledge regarding the impact of HFD during pregnancy on the neurodevelopment of the offspring.