This study investigated whether improving glycemic control and steatosis could attenuate obesity-associated dementia progression, focusing on the adenoviral protein E4orf1. 14-20-month-old APP/PS1/E4orf1 and APP/PS1 (control) mice were fed a high-fat diet. E4orf1 expression significantly improved glucose clearance, reduced insulin needs, lowered body fat, enhanced adipose tissue glucose and lipid metabolism, and reduced liver de novo lipogenesis. E4orf1 mice showed increased neurogenesis and amyloid-beta degradation gene expression and performed better in Morris Water Maze tests. The study suggests targeting glycemic control and steatosis as a potential strategy for attenuating obesity-related cognitive decline, highlighting E4orf1's potential.

Md Shahjalal Hossain Khan, Marleigh Hefner, Arubala Reddy, Nikhil V. Dhurandhar, Vijay Hegde