Obesity Improves Neuronal Metabolism and Functional Hyperemia in a Rat Model of Early Ad Pathology

Abstract

Background While obesity has been linked to both increased and decreased rate of cognitive decline in Alzheimer’s Disease (AD) patients, the interaction between obesity and AD remains largely unknown. Methods In the present study, TgF344-AD rat model was used to investigate the effects of high carbohydrate, high fat (HCHF) diet on brain glucose metabolism and brain hemodynamics in the presence or absence of AD transgenes, in pre symptomatic vs. symptomatic stages of AD progression using non-invasive brain imaging. Results In prodromal AD, HCHF had pernicious effects: it attenuated both hippocampal glucose uptake and functional hyperemia in 6-month-old nTg and TgAD rats compared to CHOW-fed cohorts. However, HCHF was beneficial in established AD: 12-month-old HCHF-fed TgAD rats showed increased hippocampal glucose uptake and amplified functional hyperemia as well as resting perfusion that was indistinguishable from that of nTg rats; the latter effect was not due to anatomical changes in hippocampal vasculature on histopathological assays. Conclusions Our findings indicate that a high caloric diet in the early stages of symptomatic AD can have propitious effects on neurophysiological and cerebrovascular function, in support of our findings that the HCHF diet stabilizes executive function in this model of AD in the early symptomatic stage of the disease. Our data provide the first hitherto evidence of the disease stage-dependent effects of high caloric diet, illuminating the brain function changes underlying the obesity paradox.