Comparative proteomic analyses of the parietal lobe from rhesus monkeys fed a high-fat/sugar diet with and without resveratrol supplementation, relative to a healthy diet: Insights into the roles of unhealthy diets and resveratrol on function

Abstract

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain.

Introduction

The Western diet has been under much scrutiny in the past couple of decades due to the abundance of saturated fat and refined sugar (HFS) content commonly used in food preparation. Long term consumption of HFS has been linked to a number of physiological conditions such as obesity, insulin resistance and type-2 diabetes mellitus, cardiac disease, ischemia, cancer, and cognitive dysfunction [1]. The projected costs of obesity-related diseases are measured not only in monetary terms, but also in life-years used to treat the disease and life-years lost to early death associated with obesity and unhealthy diets in general.

Resveratrol (RSV) is a polyphenol found primarily in red grapes, blueberries, cranberries, nuts such as peanuts and pistachios, as well as in cocoa. RSV has garnered widespread acclaim due to the many studies linking it to beneficial effects such as neuroprotection, anti-inflammation, regulation of metabolic pathways, improved glucose tolerance, and as an antioxidant [2], [3], [4], [5]. The mode of action for RSV appears to be its indirect activation of the NAD⁺-dependent deacetylase, sirtuin-1 (SIRT1), possibly through the inhibition of cyclic AMP (cAMP)-degrading phosphodiesterase, that leads to the deacetylation of the p65 subunit of NF-κB [6], [7], [8], [9].

The parietal lobe of the brain is primarily responsible for the integration of sensory information, both tactile and perceived, as well as spatial recognition and processing of both language and memory. Impairments to the parietal lobe are seen in a number of neurodegerative diseases such as Alzheimer disease (AD), Parkinson disease, and amyotrophic lateral sclerosis [10], [11], [12]. AD in particular, along with its earlier stage, amnestic-mild cognitive impairment (aMCI), have been linked to proteome dysfunction in most regions of the brain, including parietal lobule, indicating that a healthy and functioning proteome is necessary for normal brain function [13], [14]. Although there has been considerable research on the effects of RSV in a number of scenarios and models, a proteomic analysis of the primate brain has yet to be conducted. With 95% genetic homology, rhesus monkeys are an ideal translational model toward understanding the effects of a Westernized diet and the influence of RSV supplementation in a primate brain, modeling humans. Through the use of discovery-based proteomics methodology, the current study led to the identification of parietal proteins important in energy production, cellular signaling, and neurotransmission within the proteome of rhesus monkey parietal lobe which might play a role in neurodegenerative disease or dysfunction associated with an unhealthy diet.