A Short-Term Western Diet Impairs Cholesterol Homeostasis and Key Players of Beta Amyloid Metabolism in Brain of Middle Aged Rats.

Scope Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, our aim was to evaluate whether a short-term diet, rich in fat and fructose, affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers beta amyloid metabolism. Methods and results Middle aged rats (11-months old) were fed a high-fat high-fructose (HFF) or a control diet for 4 weeks. Inflammatory markers and cholesterol levels significantly increased in hippocampus of HFF rats. A higher activation of 3 hydroxy 3-methylglutaryl Coenzyme-A reductase, coupled with lower levels of Apolipoprotein E, LXR-beta, LDL-R and LRP-1 receptors was measured in hippocampus from HFF rats. The alteration of critical players of cholesterol homeostasis was associated with increased level of amyloid precursor protein, presenilin 1, and Nicastrin, and decreased level of insulin degrading enzyme. Conclusions Overall these data show that a western diet is associated with perturbation of cholesterol homeostasis in middle aged rats, mostly in hippocampus. This might prime molecular events involved in the onset of neurodegenerative diseases. This article is protected by copyright. All rights reserved.