high-fat diet-induced obesity impairs memory and alters brain protein expression in c57bl/6 mice

The impact of a high-fat diet (hfd) on hippocampal cytoskeletal and synaptic plasticity proteins remains underexplored. this study investigates how hfd-induced obesity affects the expression of key proteins involved in neuronal stability and function: microtubule-associated protein 1b (map1b), adducin-1 (add1), and ca2+/calmodulin-dependent protein kinase ii (camkii) in adolescent c57bl/6 mice. map1b and add1 play essential roles in cytoskeletal organization, while camkii is critical for synaptic plasticity and memory formation. thirty male mice were fed either an hfd for 12 weeks (hfd-12w) or 20 weeks (hfd-20w), or a standard diet (sd-12w, sd-20w) as controls. adolescence, a critical period for synaptic maturation, was chosen to examine early diet-induced neuronal alterations. body mass index (bmi) was monitored weekly, and novel object recognition tests assessed memory performance at each time point. hfd-12w mice exhibited significant bmi increases (p < 0.05), glucose intolerance, hypercholesterolemia, elevated hippocampal tumor necrosis factor-α (tnf-α) levels, and impaired recognition memory compared to sd-12w controls. in the hfd-20w group, hippocampal map1b and camkii expression decreased by 0.52-fold and 0.39-fold, respectively (p < 0.05), relative to sd-20w mice, while add1 expression remained unchanged across all groups. these findings suggest that prolonged hfd consumption disrupts cytoskeletal and synaptic plasticity proteins, potentially via neuro-inflammatory and metabolic mechanisms, leading to memory deficits. this study provides insight into how diet-induced obesity may contribute to cognitive decline, with potential relevance to metabolic disorders and neurodegenerative diseases.