Functional food lycopene mitigates obesity-related cognitive decline via lipid metabolism regulation and neuroprotection via taurine and glutathione pathway.

Obesity has emerged as a critical global public health challenge, contributing not only to metabolic disorders but also to neurological complications, including cognitive decline. Lycopene, a carotenoid found abundantly in tomatoes, has gained attention as a functional food due to its potent antioxidant and anti-inflammatory properties. This study explores the neuroprotective effects of lycopene against obesity-related cognitive impairment in male C57BL/6 mice. Mice were fed a high-fat diet (HFD) for four months to induce obesity, followed by supplementation with lycopene (50 mg/kg). Cognitive performance was assessed through Y-maze, Morris water maze, and novel object recognition tests. We also examined systemic and hippocampal inflammatory markers, along with lipidomic and proteomic profiles. Lycopene supplementation significantly improved cognitive function, restored neuronal density, and enhanced levels of key neuroprotective proteins, including BDNF and NeuN. Lipidomic analysis revealed a reduction in pro-inflammatory lipids (e.g., lysophosphatidylcholine, triglycerides) and an increase in neuroprotective lipids (e.g., phosphatidylserine, fatty acids). Additionally, proteomic data showed a decrease in lipid-induced neurotoxic proteins and an upregulation of pathways associated with taurine and glutathione metabolism, promoting neuronal stability and plasticity. These results suggest that lycopene exerts neuroprotective effects by restoring lipid balance and modulating amino acid signaling pathways, thereby alleviating cognitive decline in obese mice. This study highlights lycopene's potential as a functional dietary ingredient to combat obesity-related neurological disorders and provides novel insights into the development of food-based strategies to improve both metabolic health and cognitive function.