Association between cognitive impairment promoted by high-fat diet and increase in PTEN phosphorylation

The purpose of this study was to observe the changes in memory impairment and hippocampal phosphorylated protein levels in mice caused by obesity, and to explore the key phosphorylation modification proteins and pathways of memory impairment induced by high-fat diet. First, sixteen C57BL/6 J mice were randomly divided into simple obese group (group H, n = 8) and normal control group (group C, n = 8). And at the end of the experiment, the cognitive function of the mice was assessed by Morris water maze and serological indexes were measured. Finally, phosphoproteomics was used to identify the differentially phosphorylted protein expression in the hippocampus of obese mice. Compared with group C, mice in group H had significantly decreased learning and memory abilities, and significantly increased body weight, blood glucose and lipid levels. The results of the phosphoproteomics analysis showed 442 up-regulated differentially phosphorylated proteins and 402 down-regulated differentially phosphorylated proteins. Further protein-protein interaction (PPI) analysis revealed pathway hub proteins, including β-actin (ACTB), Phosphatase and tensin homolog deleted on chromosome ten (PTEN), Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), mammalian target of rapamycin (mTOR), ribosomal protein 6 (RPS6), etc. Notably, the hub proteins PTEN, PIK3R1, and mTOR were jointly involved in the mTOR signaling pathway. Our study shows for the first time that a high-fat diet increases the phosphorylation of PTEN proteins, which may affect cognitive function.