Diet-induced obesity suppresses expression of many proteins at the blood-brain barrier.
The blood-brain barrier (BBB) is a regulatory interface between the central nervous system and the rest of the body. However, BBB changes in obesity and metabolic syndrome have not been fully elucidated. We hypothesized that obesity reduces energy metabolism in the cerebral microvessels composing the BBB, reflected by downregulation of protein expression and function. We performed comparative proteomic analyses in enriched microvessels from the cerebral cortex of mice 2 months after ingestion of a high-fat diet or regular rodent chow. In mice with diet-induced obesity (DIO), there was downregulation of 47 proteins in the cerebral microvessels, including cytoskeletal proteins, chaperons, enzymes, transport-related proteins, and regulators for transcriptional and translational activities. Only two proteins, involved in messenger RNA (mRNA) transport and processing, were upregulated. The changes of these proteins were further validated by quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescent staining of freshly isolated microvessels, in samples obtained from different batches of mice. The predominant downregulation suggests that DIO suppresses metabolic activity of BBB microvessels. The finding of a hypometabolic state of the BBB in mice at the chronic stage of DIO is unexpected and unprecedented; it may provide novel mechanistic insight into how obesity influences CNS function via regulatory changes of the BBB.
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Suidong
S
Ouyang
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Hung
H
Hsuchou
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Abba J
AJ
Kastin
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Yuping
Y
Wang
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Chuanhui
C
Yu
Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Weihong
W
Pan
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation