دورية أكاديمية
أعرض في EDS

Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation.

التفاصيل البيبلوغرافية
العنوان: Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation.
المؤلفون: Desai HR; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada., Sivasubramaniyam T; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Revelo XS; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Schroer SA; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Luk CT; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Rikkala PR; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Metherel AH; Department of Nutritional Sciences, University of Toronto, Toronto, M5S 3E2, Canada., Dodington DW; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Park YJ; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Kim MJ; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada.; Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, Korea., Rapps JA; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Besla R; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada., Robbins CS; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada.; Peter Munk Cardiac Centre, University Health Network, Toronto, M5G 1L7, Canada., Wagner KU; Eppley Institute for Research in Cancer and Allied Diseases and the Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, 68198, USA., Bazinet RP; Department of Nutritional Sciences, University of Toronto, Toronto, M5S 3E2, Canada., Winer DA; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada.; Department of Pathology, University Health Network, Toronto, M5G 2C4, Canada., Woo M; Toronto General Hospital Research Institute, University Health Network, Toronto, M5G 1L7, Canada. mwoo@uhnresearch.ca.; Division of Endocrinology and Metabolism, Department of Medicine, University Health Network and University of Toronto, Toronto, M5G 2C4, Canada. mwoo@uhnresearch.ca.
المصدر: Scientific reports [Sci Rep] 2017 Aug 09; Vol. 7 (1), pp. 7653. Date of Electronic Publication: 2017 Aug 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Diet, High-Fat*/adverse effects, Inflammation/*etiology , Janus Kinase 2/*deficiency , Macrophages/*metabolism, Adipocytes/metabolism ; Adipocytes/pathology ; Animals ; Chemokines/genetics ; Chemokines/metabolism ; Disease Models, Animal ; Gene Expression ; Hypertrophy ; Inflammation/metabolism ; Inflammation/pathology ; Insulin Resistance/genetics ; Intra-Abdominal Fat/metabolism ; Liver/metabolism ; Macrophages/immunology ; Male ; Mice ; Mice, Knockout ; Myeloid Cells/immunology ; Myeloid Cells/metabolism
مستخلص: During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2 -/- ) mice gained less body weight compared to wildtype littermate control (M-JAK2 +/+ ) mice and were protected from HFD-induced systemic insulin resistance. Histological analysis revealed smaller adipocytes and qPCR analysis showed upregulated expression of some adipogenesis markers in visceral adipose tissue (VAT) of HFD-fed M-JAK2 -/- mice. There were decreased crown-like structures in VAT along with reduced mRNA expression of some macrophage markers and chemokines in liver and VAT of HFD-fed M-JAK2 -/- mice. Peritoneal macrophages from M-JAK2 -/- mice and Jak2 knockdown in macrophage cell line RAW 264.7 also showed lower levels of chemokine expression and reduced phosphorylated STAT3. However, leptin-dependent effects on augmenting chemokine expression in RAW 264.7 cells did not require JAK2. Collectively, our findings show that macrophage JAK2 deficiency improves systemic insulin sensitivity and reduces inflammation in VAT and liver in response to metabolic stress.
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المشرفين على المادة: 0 (Chemokines)
EC 2.7.10.2 (Janus Kinase 2)
تواريخ الأحداث: Date Created: 20170811 Date Completed: 20190225 Latest Revision: 20190225
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5550513
DOI: 10.1038/s41598-017-07923-0
PMID: 28794431
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-017-07923-0