Resveratrol Supplementation Ameliorates Neuronal Insults in Cortical Brain Tissue of Nonhuman Primates Fed a High-Fat/Sucrose Diet

Chronic high-fat/high-sugar (HFS) feeding is linked to the development of insulin resistance as well as arterial wall and adipose tissue inflammation in nonhuman primates. These changes are significantly reduced when the animals are fed a HFS diet supplemented with resveratrol (RSV) for two years. Herein, we evaluated the occurrence of cerebral cortex injury in these HFS-fed middle-aged male rhesus monkeys and investigated the possibility of brain protection by RSV treatment. HFS caused a reduction in capillary density in the cerebral cortex that was preempted by RSV supplementation. The patterns of cDNA microarray analysis revealed upregulation of markers of oxidative stress, inflammation and apoptosis in the cortical cortex of HFS-fed monkeys, which was reversed by RSV. The underlying mechanism of RSV action included its ability to prevent the HFS-mediated NF-kappa-B activation and loss in mitochondrial aldehyde dehydrogenase 2 expression. We conclude that RSV may confer neuroprotection against HFS-mediated cerebral vascular dysfunction and activation of inflammatory pathways. Twenty-four adult (7-13 years old) male rhesus monkeys (Macaca mulatta) were maintained on standard NIH monkey chow (Purina Mills) during baseline assessment, and then quasi-randomized (such that average age and bodyweight did not differ significantly between groups) to one of three two-year dietary regimens: Four animals were fed a healthy standard diet (SD) with 13% Kcal in fat and less than 5% sucrose by weight, ten animals were fed a high fat and sugar (HFS) diet with 42% Kcal in fat and 27% sucrose by weight (Harlan, Teklad), and another ten animals (RESV) were fed the same HFS diet plus a flavored primate treat (Bioserve) containing 40 mg and 240 mg resveratrol (RSV) twice daily, during year 1 and 2, respectively. Monkeys in non-RSV groups received placebo treats.