Changes of Blood-Brain Barrier and Brain Parenchymal Protein Expression Levels of Mice under Different Insulin-Resistance Conditions Induced by High-Fat Diet

PurposeThe purpose of the present study was to investigate changes of blood-brain barrier (BBB) and brain parenchymal protein expression due to type II diabetes mellitus (T2DM) induced by a high-fat diet (HFD) by using SWATH-based quantitative proteomics.MethodsMice were fed a HFD for 2 or 10weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed.ResultsIn brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2weeks, but recovered to the levels in the normal diet (ND) group at 10weeks. P-glycoprotein function at the BBB was reduced at 2weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2weeks, but recovered at 10weeks.ConclusionOur results suggest that changes in the status of insulin resistance influence expression of BBB transporters, which in turn may alter the expression of cognitive function-related proteins.