Western diet combined with rosmarinic acid in old mice exerts negative effects on metabolism but improves cognitive and emotional behaviour in a sex-dependent fashion

Leuven, Belgium. Bad nutritional habits may accelerate the aging process by disrupting energy metabolism, with non-negligible carry-over effects on emotional and cognitive behaviour. The lack of target-specific drugs able to counteract age-related physical and cognitive decline makes the use of nutraceuticals an appealing alternative strategy. We investigated the ability of the nutraceutical compound rosmarinic acid (RA) to counteract the negative effects of a Western Diet (WD), high in sugar and fat, in a murine model of aging. Male and female 22-month-old C57BL/6N mice were treated either with RA (500 mg/kg daily) or vehicle (KH2PO4/K2HPO4) via drinking water. Two weeks later, all subjects received either WD or control diet for 28 days and were tested for emotional (Elevated Plus Maze - EPM), cognitive (Morris Water Maze - MWM) and metabolic parameters. While preventing the WD-induced increase in body weight in males, RA failed to counteract the negative effects of WD on glucose metabolism, leading also to negative effects on the lipid profile. Surprisingly, in the MWM, WD improved learning in males and memory in females. In the EPM, while WD increased exploration in females, RA reduced emotionality in males. Overall, our data suggest that a high fat-high sugar diet exerts both negative (metabolism) and positive (behaviour) effects in old mice in a sex-dependent fashion. RA showed limited ability to counteract the negative effects of WD on metabolism, while improving the emotional profile of male mice, an effect that deserves to be investigated further. Support: H2020 AwE (grant N. 633589).