Sex Differences in The Effect of Long-Term High-FatDiet on Brain Glucose Metabolism and Expression of Alzheimer'sRelated Genes in Wistar Rat

Objective: High fat diet is reportedly associated with insulinresistance, neuroinflammation and blood-brain barrier impairment,all postulated as risk factors for Alzheimer’s disease. Thisstudy investigates whether long-term high-fat diet (HFD) causesglucose metabolism changes and Alzheimer's-like pathologyin a sex-dependent manner in rats when compared with normalchow diet (NCD) intake.Materials and Methods: After weaning, twenty male and femalerats were randomly fed HFD (۵۵.۹% fat) or NCD (۱۰%fat) for ۱۶-weeks. Behavioral tests for spatial memory assessmentand ۱۸F-FDG-PET-scan were performed in the two last weeks of experiments. All rats were then euthanized and hippocampaltissues were collected to assess gene expression byqPCR.Result: Evaluating spatial learning and memory by Morris watermaze showed that while the effect of training is significantin all the four groups, memory retrieval measured by the latencyto find the hidden platform and the frequency crossingof the platform, is impaired in HFD male rats compared to correspondingcontrol. In Y-maze test, HFD male rats showed asignificant decrease in spontaneous alternation and increase inalternate arm returns. In addition, measuring ۱۸F-FDG uptakein the whole brain revealed a significant reduction in glucosemetabolism in male but not female HFD rats. Analysis of ۸candidate Alzheimer’s related genes including InsR, GLUT۱,IDE, BACE۱, APP, PSEN۱, PSEN۲, and BDNF showed thathippocampal expression of GLUT۱ and IDE is significantlychanged only in HFD male rats.Conclusions: Our results suggest that sex interferes with thehigh-fat diet-induced dysregulation of brain glucose metabolism,and memory impairment

کلیدواژه ها:

Alzheimer’s Disease ، Brain Glucose Metabolism ، High-Fat Diet