Public Health & Health Science Division, ULAB

Childhood obesity and metabolic disorders have risen sharply as the consumption ofhigh-fat diets (HFDs) increases, yet the neurocognitive consequences - specifically during the juvenile development window - remain under-researched. This paper synthesizes current literature to examine how HFD-induced metabolic shifts suppress brain-derived neurotrophic factor (BDNF) in the hippocampus, leading to impaired learning and memory independent of body weight. Our analysis identifies dual-pathway mechanism of suppression: first, HFD-driven gut dysbiosis reduces the production of microbial short-chain fatty acids (SCFAs), particularly butyrate, hence limiting the histone deacetylase (HDAC) inhibition required for BDNF gene expression. Second, HFD consumption chronically elevates corticosterone levels, which directly downregulates BDNF mRNA and increases neuroinflammation. Synthesis of rodent modelsreveals that these molecular changes manifest as structural hippocampal shrinkage andbehavioral deficits in juvenile populations. While limitations exist regarding animal-to-human translation, these findings underscore a “metabo-psychiatric” crisis where early dietarycomposition impacts long-term cognitive health. We conclude that interventions targeting the gut-brain axis, such as precision prebiotic nutrition, may be essential to mitigate the neurodevelopmental risks of HFD.