title: Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia.
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.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: tsune-ta@med.nagoya-u.ac.jp.
authors.forename: Taku
authors.initials: T
authors.lastname: Tsunekawa
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: ryouichi@med.nagoya-u.ac.jp.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: mizoguchi.akira@med.nagoya-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: sugiyama.mariko@med.nagoya-u.ac.jp.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: t999tommy@med.nagoya-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: t-onoue@med.nagoya-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Onoue
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: d-hagiwara@med.nagoya-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: yoshi716@med.nagoya-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464-8601, Japan. Electronic address: siwama@med.nagoya-u.ac.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Iwama
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: goto@med.nagoya-u.ac.jp.
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: sugahide@med.nagoya-u.ac.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: sugiyosi@med.nagoya-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: arima105@med.nagoya-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse
keywords: High fat diet; Hypothalamic inflammation; Microglia; Obesity; Protein tyrosine phosphatase-1B; Signal transducer and activator of transcription-3