Abstract
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 (54 μg/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 (1H 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. Interestingly, these results allowed us to determine a sequence in brain impairments; first, micro structural changes, followed by metabolic disturbances and later on morphological modifications.