Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut-liver-brain axis

Background/objectives The aim of the current study was to investigate the inhibitory effect of lycopene (LYC), a major carotenoid present in tomato, on high-fat and high-fructose western diet (HFFD)-induced cognitive impairments and the protective effects on HFFD-elicited insulin resistance, lipid metabolism dysfunction and inflammatory responses in the gut-liver-brain axis. Subjects/methods We randomly assigned 3-month-old C57BL/6J mice to three groups with different diets: the control group, HFFD group and HFFD + LYC group (LYC, 0.03% w/w, mixed into high-fat diet) for 10 weeks. Results The results of the Y-maze task and Morris water maze tests demonstrated that LYC attenuated HFFD-induced memory loss. Moreover, LYC suppressed HFFD-elicited synaptic dysfunction and increased the expressions of SNAP-25 and PSD-95. Furthermore, LYC ameliorated insulin resistance, lipid metabolism dysfunction and inflammatory responses in the mouse brain and liver. LYC also prevente. d intestinal barrier integrity damages and decreased the level of circulating LPS. Conclusions These results demonstrated that LYC ameliorated HFFD-induced cognitive impairments in a mouse model by improving insulin resistance, lipid metabolism dysfunction and inflammatory responses in the gut-liver-brain axis. These findings indicate that LYC might be a nutritional strategy for western diet-induced dysfunction of the central nervous system.