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Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia.
- Source :
-
EBioMedicine [EBioMedicine] 2017 Feb; Vol. 16, pp. 172-183. Date of Electronic Publication: 2017 Jan 09. - Publication Year :
- 2017
-
Abstract
- Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions.<br /> (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Diet, High-Fat adverse effects
Enzyme Activation
Female
Gene Expression
Hypothalamus pathology
Inflammation etiology
Inflammation genetics
Interleukin-10 genetics
Interleukin-10 metabolism
Male
Mice, Knockout
Microscopy, Confocal
Organ Culture Techniques
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Hypothalamus metabolism
Inflammation metabolism
Janus Kinase 2 metabolism
Microglia metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 1 deficiency
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 16
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 28094236
- Full Text :
- https://doi.org/10.1016/j.ebiom.2017.01.007