Gene Expression Profiling in the Cortex of Fabp4 Knockout Mice

Aims: Fatty acid binding protein 4, adipocyte (Fabp4), is well known for its role in peripheral lipid metabolism, but its potential role in brain function remains largely unexplored. This study aimed to investigate Fabp4 expression in the adult mouse brain and explore gene expression changes in Fabp4 knockout (KO) mice to assess its potential impact on brain function. Methods: We conducted in situ hybridization to assess Fabp4 expression in key brain regions of adult mice. In parallel, differential gene expression analysis using RNA-seq was conducted in the prefrontal cortex of Fabp4 KO mice to identify genes affected by Fabp4 deficiency. Results: No Fabp4 expression was detected in the brains of mice, suggesting a lack of direct involvement in the central nervous system. However, Fabp4 KO mice exhibited significant changes in gene expression in the brain, with 31 genes upregulated and 30 downregulated. Downregulated genes were linked to histone methylation and metabolic processes, while upregulated ones were associated with synaptic organization. Conclusion: Although Fabp4 is not expressed in the brain, its deficiency leads to substantial changes in gene expression, likely mediated by peripheral metabolic pathways and epigenetic regulation. These changes may explain the previously observed autism-like behaviors and increased dendritic spine density in Fabp4 KO mice. This study sheds light on the role of systemic lipid metabolism in neurodevelopmental disorders such as autism spectrum disorder (ASD) and highlights epigenetic mechanisms as potential mediators of these effects.