High-fructose diet enhances cerebral neurodegenerative process; preventive effect of resveratrol. A nuclear magnetic resonance imaging and spectroscopy study on rat nutritional models

Insulin resistance (IR) could play a role in neurodegenerative diseases (ND). The high-fructose (HF) diet is an IR model in rats. The vitamin A-deprived (VAD) rat is known to develop large similarities with ND within only 14 weeks post-weaning. Since VAD symptoms are partly reversible and independent of any IR mechanism, this ND model was used to investigate (i) a potential additional effects of IR in a ND context, and (ii) a possible preventive strategy when resveratrol (RSV) is added to the diet. Male Wistar rats were fed from weaning to 15-19 weeks: control, HF (60%), VAD and a combination HF+VAD; some control, VAD and VAD + HF rats were force-fed with trans-RSV (54g/100 g weight). In addition to assessing blood parameters (IR or inflammation), nuclear magnetic resonance (NMR) allowed both: (i) a longitudinal follow-up of brain anatomical (MRI) and early micro-structural changes (diffusion tensor imaging) and (ii) a metabolomic study of brain and liver ( 1 H HRMAS spectroscopy) at key points in the diets. An early decrease (<6 weeks) in fractional anisotropy in hippocampus was evidenced in VAD and preceded other impairments. HF diet induced biological IR from week 9 but brain metabolomic changes were already detected from week 5. In contrast, no brain morphologic change was observed. VAD + HF diet impaired rat health, enhanced the retinolemia VAD-induced decrease and increased ventricular volume vs both HF and VAD. Presence of RSV decreased IR, maintained retinol and attenuated the ventricular volume increase, probably via AMPKinase activation.