CHRONIC HIGH-FAT DIET CONSUMPTION INCREASES PERIPHERAL ADIPOKINES WHILE IMPROVING HIPPOCAMPAL NEURONAL PLASTICITY AND COGNITIVE ABILITIES IN ADULT FEMALE MICE

Chronic consumption of a high-fat diet (HFD) has been associated with increased systemic low-grade inflammation. This state may trigger brain inflammation, ultimately increasing susceptibility to psychiatric disorders and behavioral alterations. We hypothesize that such immune activation may specifically affect brain functioning by impairing neuronal plasticity.
Thirty-one female C57/Bl6 mice were housed in the IntelliCage, an automated system with four operant chambers in the corners, to evaluate the effect of a 4-week HFD administration on cognitive abilities using the place learning test. Circulating levels of adipokines (i.e., leptin, adiponectin) were measured through ELISA. Hippocampal plasticity was evaluated via LTP at Schaffer collateral-CA1 synapses.
HFD consumption led to increased body weight, increased leptin and reduced adiponectin. When assessing cognitive abilities, both the CD and HFD groups gradually increased their visits to the target corner in the acquisition phase of the place learning test. However, in the reversal phase, where the target corner position is switched to the opposite side compared to the acquisition phase, HFD-fed mice exhibited fewer errors, suggesting improved extinction ability. Electrophysiological recordings showed that HFD induced an enhancement of LTP amplitude at Schaffer collateral-CA1 synapses after two stimulation trains.
Overall, our data suggest that adult consumption of an HFD affects behavioral flexibility and hippocampal plasticity, increasing adipokine signalling. We are currently assessing the immuno-metabolic profile of each individual to unravel the mechanisms underlying these effects.
Funding: European Union -Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and strengthening of biomedical research in the NHS.