Journal Article

DZNE-2020-02833

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Toll-like receptors 2 and 4 impair insulin-mediated brain activity by interleukin-6 and osteopontin and alter sleep architecture.

Sartorius, T. ; Lutz, S. Z. ; Hoene, M. ; Waak, J.DZNE* ; Peter, A. ; Weigert, C. ; Rammensee, H.-G. ; Kahle, P. J.DZNE* ; Häring, H.-U. (Corresponding author) ; Hennige, A. M.

2012
FASEB Bethesda, Md.

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Please use a persistent id in citations: doi:10.1096/fj.11-191023

Abstract: Impaired insulin action in the brain represents an early step in the progression toward type 2 diabetes, and elevated levels of saturated free fatty acids are known to impair insulin action in prediabetic subjects. One potential mediator that links fatty acids to inflammation and insulin resistance is the Toll-like receptor (TLR) family. Therefore, C3H/HeJ/TLR2-KO (TLR2/4-deficient) mice were fed a high-fat diet (HFD), and insulin action in the brain as well as cortical and locomotor activity was analyzed by using telemetric implants. TLR2/4-deficient mice were protected from HFD-induced glucose intolerance and insulin resistance in the brain and displayed an improvement in cortical and locomotor activity that was not observed in C3H/HeJ mice. Sleep recordings revealed a 42% increase in rapid eye movement sleep in the deficient mice during daytime, and these mice spent 41% more time awake during the night period. Treatment of control mice with a neutralizing IL-6 antibody improved insulin action in the brain as well as cortical activity and diminished osteopontin protein to levels of the TLR2/4-deficient mice. Together, our data suggest that the lack of functional TLR2/4 protects mice from a fat-mediated impairment in insulin action, brain activity, locomotion, and sleep architecture by an IL-6/osteopontin-dependent mechanism.

Keyword(s): Animals (MeSH) ; Astrocytes: metabolism (MeSH) ; Brain: physiology (MeSH) ; Cells, Cultured (MeSH) ; Electroencephalography (MeSH) ; Glucose Tolerance Test (MeSH) ; Insulin: physiology (MeSH) ; Insulin Resistance (MeSH) ; Interleukin-6: immunology (MeSH) ; Interleukin-6: physiology (MeSH) ; Locomotion (MeSH) ; Mice (MeSH) ; Mice, Inbred C3H (MeSH) ; Mice, Knockout (MeSH) ; Osteopontin: physiology (MeSH) ; Phosphorylation (MeSH) ; Proto-Oncogene Proteins c-akt: metabolism (MeSH) ; Real-Time Polymerase Chain Reaction (MeSH) ; Sleep (MeSH) ; Toll-Like Receptor 2: genetics (MeSH) ; Toll-Like Receptor 2: physiology (MeSH) ; Toll-Like Receptor 4: genetics (MeSH) ; Toll-Like Receptor 4: physiology (MeSH) ; Insulin ; Interleukin-6 ; Tlr2 protein, mouse ; Tlr4 protein, mouse ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Osteopontin ; Proto-Oncogene Proteins c-akt

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Contributing Institute(s):

1. Functional Neurogenetics (AG Kahle 2)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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