THE EFFECT OF RESVERATROL SUPPLEMENTATION ON THE EFFECTS OF A HIGH-FAT DIET IN A 3XTGAD FEMALE MOUSE MODEL OF ALZHEIMER'S DISEASE

Abstract

Background:Mid-life obesity can increase the risk for developing dementia later in life, particularly Alzheimer’s disease (AD), and experimental diet-induced obesity increases AD-like pathology and/or behavioural deficits in transgenic mouse models of AD. However, most of these experimental studies assess the effect of high fat diet (HFD) in male mice only, and effects in female mice are less clear. Moreover, our previous work has shown that HFD also affects memory in healthy controls and that this effect is gender dependent.Resveratrol (RSV) has recently showed to improve health and life span of mice on a HFD and to improve learning and memory in both aged and AD mice, effects that are thought to be due to its anti-oxidant and/or anti-inflammatory properties. However until now no studies have been done taking into account both AD and co-morbidities (obesity). Therefore, the aim of this study was to test the effect of RSV in female 3xTgADmice fed with a HFD.Methods:Groups of female 3xTgAD and control (Non-Tg) mice w ere maintained on a control (12% fat) or a HFD (60% fat) for 12 months with or without RSV supplementation in the drinking water (5 mg/Kg/day). Body weight (BW) was monitored weekly. Behaviour was assessed at 12 months of treatment using the open-field and Y-maze spontaneous alternation tests. Epididymal fat, brown adipose tissue (BAT) and liver weight were measured after culling.Results: RSV did not affect BW in female 3xTgADmice fed a HFD but a decrease in weight gain was observed in Non-Tg HFD animals. HFD increased epididymal fat and BAT weight in both Non-Tg and 3xTgAD mice, and RSV reversed this effect only in Non-Tg mice. HFD also elevated liver weight in Non-Tg mice, which was reversed by RSV. RSV had no effect on behaviour or memory in both groups. Conclusions: These results suggest that RSV is able to reverse metabolic changes induced by the HFD in female Non-Tg mice but not in 3xTgAD animals, with no effect on behaviour in either. In conclusion, the effect of a HFD on memory is not affected by RSV and therefore is unlikely to be due to changes in oxidative stress and/or inflammation.