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

Abstract 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 stud...

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Autores principales:	Harsh R. Desai, Tharini Sivasubramaniyam, Xavier S. Revelo, Stephanie A. Schroer, Cynthia T. Luk, Prashanth R. Rikkala, Adam H. Metherel, David W. Dodington, Yoo Jin Park, Min Jeong Kim, Joshua A. Rapps, Rickvinder Besla, Clinton S. Robbins, Kay-Uwe Wagner, Richard P. Bazinet, Daniel A. Winer, Minna Woo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b77b851e7bc64e208ba3be8fd1060be7
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spelling	oai:doaj.org-article:b77b851e7bc64e208ba3be8fd1060be72021-12-02T12:31:58ZMacrophage JAK2 deficiency protects against high-fat diet-induced inflammation10.1038/s41598-017-07923-02045-2322https://doaj.org/article/b77b851e7bc64e208ba3be8fd1060be72017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07923-0https://doaj.org/toc/2045-2322Abstract 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.Harsh R. DesaiTharini SivasubramaniyamXavier S. ReveloStephanie A. SchroerCynthia T. LukPrashanth R. RikkalaAdam H. MetherelDavid W. DodingtonYoo Jin ParkMin Jeong KimJoshua A. RappsRickvinder BeslaClinton S. RobbinsKay-Uwe WagnerRichard P. BazinetDaniel A. WinerMinna WooNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Harsh R. Desai Tharini Sivasubramaniyam Xavier S. Revelo Stephanie A. Schroer Cynthia T. Luk Prashanth R. Rikkala Adam H. Metherel David W. Dodington Yoo Jin Park Min Jeong Kim Joshua A. Rapps Rickvinder Besla Clinton S. Robbins Kay-Uwe Wagner Richard P. Bazinet Daniel A. Winer Minna Woo Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
description	Abstract 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.
format	article
author	Harsh R. Desai Tharini Sivasubramaniyam Xavier S. Revelo Stephanie A. Schroer Cynthia T. Luk Prashanth R. Rikkala Adam H. Metherel David W. Dodington Yoo Jin Park Min Jeong Kim Joshua A. Rapps Rickvinder Besla Clinton S. Robbins Kay-Uwe Wagner Richard P. Bazinet Daniel A. Winer Minna Woo
author_facet	Harsh R. Desai Tharini Sivasubramaniyam Xavier S. Revelo Stephanie A. Schroer Cynthia T. Luk Prashanth R. Rikkala Adam H. Metherel David W. Dodington Yoo Jin Park Min Jeong Kim Joshua A. Rapps Rickvinder Besla Clinton S. Robbins Kay-Uwe Wagner Richard P. Bazinet Daniel A. Winer Minna Woo
author_sort	Harsh R. Desai
title	Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
title_short	Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
title_full	Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
title_fullStr	Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
title_full_unstemmed	Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
title_sort	macrophage jak2 deficiency protects against high-fat diet-induced inflammation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b77b851e7bc64e208ba3be8fd1060be7
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Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation

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