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

Autor:	Rickvinder Besla, Kay Uwe Wagner, Yoo Jin Park, Stephanie A. Schroer, Clinton S. Robbins, Min Jeong Kim, Daniel A. Winer, Richard P. Bazinet, Prashanth R. Rikkala, Tharini Sivasubramaniyam, Cynthia T. Luk, David W. Dodington, Joshua A. Rapps, Harsh R. Desai, Adam H. Metherel, Minna Woo, Xavier S. Revelo
Jazyk:	angličtina
Rok vydání:	2017
Předmět:	0301 basic medicine Male medicine.medical_specialty Chemokine Science Adipose tissue Gene Expression Inflammation Intra-Abdominal Fat Diet High-Fat Article 03 medical and health sciences Mice Insulin resistance Downregulation and upregulation Internal medicine hemic and lymphatic diseases medicine Adipocytes Macrophage Animals Myeloid Cells Mice Knockout Gene knockdown Multidisciplinary biology Macrophages food and beverages Hypertrophy Janus Kinase 2 medicine.disease Disease Models Animal 030104 developmental biology Endocrinology Liver Adipogenesis biology.protein Medicine medicine.symptom Chemokines Insulin Resistance hormones hormone substitutes and hormone antagonists
Zdroj:	Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
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