The Association Between Vegetarian Diet and Healthy Aging Among Chinese Older Adults

Objectives: Insulin resistance plays a central pathophysiological role in obesity, type 2 Diabetes (T2D), and Alzheimer's Disease (AD).Insulin resistance characterized by hyperglycemia and hyperinsulinemia, contribute to AD by increasing advanced glycation end products (AGEs), impairing synaptic plasticity, and promoting oxidative stress and neuroinflammation.Novel adenoviral protein E4orf1, improves glycemic control and protects against liver fat accumulation despite obesity.We hypothesize that by targeting insulin-related risk factors, E4orf1 delays AD onset and progression.We previously showed that E4orf1 enhances metabolic function and cognition in an older AD mouse model.Here we determined the systemic and molecular effects of E4orf1 protein in male mice with an obesity-related transgenic mouse model of AD expressing APP/PS1 genes.Methods: Four-to six-month-old male mice WT (n10), APP/PS1 (n8), and APP/PS1 expressing E4orf1 (n12) underwent baseline systemic (body weight, EchoMRI, oral glucose tolerance test, insulin, hemoglobin A1c) and behavioral (Y-maze and Morris Water Maze (MWM)) analyses, following, which mice were placed on a 60% high-fat diet.Four months later, analyses were repeated, and mice sacrificed.Tissues were collected for molecular pathway analysis in liver and adipose tissue via RT-qPCR.Results: Although APP/PS1 mice are AD prone, E4orf1 expression significantly reduced HbA1c, lowered endogenous insulin requirements for glucose clearance, decreased body weight, and improved habituation and spatial memory in Y-Maze and MWM tests, compared to APP/PS1 controls, despite a high-fat diet.In the liver, E4orf1 lowered gene expression related to lipogenesis, fatty acid transport, and triglyceride synthesis.In adipose tissue, it significantly increased genes associated with fatty acid transport and -oxidation.Conclusions: At present, there is no cure for AD, and existing treatments are limited to symptom management.E4orf1 has the potential to serve as an insulin-independent therapeutic agent for obesity-associated AD.