In a recent issue of Diabetes, Vandal et al. (1) showed that the administration of a high-fat diet induced the deposition of β-amyloid in the brains of mice. They also showed that the deposition of amyloid was prevented or reversed by the administration of insulin. These observations are consistent with our previous observation that morbid obesity in the human is associated with an increase in the expression of amyloid precursor protein (APP) in circulating mononuclear cells along with other indices of inflammation and that the expression of APP and other inflammatory mediators diminishes after weight loss following gastric bypass surgery (2). In addition, we have also shown that an insulin infusion for a short duration (4 h) suppresses the expression of APP protein and mRNA (3). In addition, there was also a suppression of presenilins and GSK3β, key proteins involved in the pathogenesis of Alzheimer disease (AD). On the other hand, we were not able to demonstrate the induction of APP in our simple model of diet-induced inflammation involving the intake of a 900 calorie high-fat, high-carbohydrate meal. This meal also induces a series of proteins that interfere with insulin signaling: SOCS3, PTP-1B, JNK-1, and p38 MAPK (4). It is, however, of interest that an equicaloric meal rich in fruit and fiber does not induce inflammation and oxidative stress (4), consistent with the recent observation that Mediterranean diets may be protective to AD (5). It is likely that the intake of high-calorie and high-fat diets over a prolonged period is necessary to induce an increased expression of amyloid. Clearly, such a model needs to be tested to establish a relationship between diet, obesity, insulin resistance, and AD, as AD is more common in obesity and type 2 diabetes.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.