TY - JOUR
T1 - Changes of Blood-Brain Barrier and Brain Parenchymal Protein Expression Levels of Mice under Different Insulin-Resistance Conditions Induced by High-Fat Diet
AU - Ogata, Seiryo
AU - Ito, Shingo
AU - Masuda, Takeshi
AU - Ohtsuki, Sumio
N1 - Funding Information:
We are grateful for partial financial support in the form of three Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (JSPS) and a Grant-in-Aid for Scientific Research on Innovative Areas (15H01562), as well as a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Ohtsuki S is a full professor at Kumamoto University and is also a director of Proteomedix Frontiers. This study was not supported by the company, and his position at the company did not influence the design of the study, the collection of the data, the analysis or interpretation of the data, the decision to submit the manuscript for publication, or the writing of the manuscript, and did not present any financial conflicts. The other authors declare no competing interests.
Funding Information:
We are grateful for partial financial support in the form of three Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (JSPS) and a Grant-in-Aid for Scientific Research on Innovative Areas (15H01562), as well as a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Ohtsuki S is a full professor at Kumamoto University and is also a director of Proteomedix Frontiers. This study was not supported by the company, and his position at the company did not influence the design of the study, the collection of the data, the analysis or interpretation of the data, the decision to submit the manuscript for publication, or the writing of the manuscript, and did not present any financial conflicts. The other authors declare no competing interests.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Purpose: The 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. Methods: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. Results: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. Conclusion: Our 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.
AB - Purpose: The 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. Methods: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. Results: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. Conclusion: Our 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.
KW - Blood-brain barrier
KW - central nervous system
KW - insulin resistance
KW - quantitative proteomics
KW - type II diabetes mellitus
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U2 - 10.1007/s11095-019-2674-8
DO - 10.1007/s11095-019-2674-8
M3 - Article
C2 - 31367840
AN - SCOPUS:85070008523
SN - 0724-8741
VL - 36
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 10
M1 - 141
ER -
