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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number7653
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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High Fat Diet
Intra-Abdominal Fat
Macrophages
Inflammation
Insulin Resistance
Chemokines
Obesity
Adipogenesis
Physiological Stress
Liver
Peritoneal Macrophages
Leptin
Crowns
Adipocytes
Intercellular Signaling Peptides and Proteins
Body Weight
Cytokines
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Desai, H. R., Sivasubramaniyam, T., Revelo, X. S., Schroer, S. A., Luk, C. T., Rikkala, P. R., ... Woo, M. (2017). Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. Scientific Reports, 7(1), [7653]. https://doi.org/10.1038/s41598-017-07923-0

Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. / Desai, Harsh R.; Sivasubramaniyam, Tharini; Revelo, Xavier S.; Schroer, Stephanie A.; Luk, Cynthia T.; Rikkala, Prashanth R.; Metherel, Adam H.; Dodington, David W.; Park, Yoo Jin; Kim, Min Jeong; Rapps, Joshua A.; Besla, Rickvinder; Robbins, Clinton S.; Wagner, Kay Uwe; Bazinet, Richard P.; Winer, Daniel A.; Woo, Minna.

In: Scientific Reports, Vol. 7, No. 1, 7653, 01.12.2017.

Research output: Contribution to journalArticle

Desai, HR, Sivasubramaniyam, T, Revelo, XS, Schroer, SA, Luk, CT, Rikkala, PR, Metherel, AH, Dodington, DW, Park, YJ, Kim, MJ, Rapps, JA, Besla, R, Robbins, CS, Wagner, KU, Bazinet, RP, Winer, DA & Woo, M 2017, 'Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation', Scientific Reports, vol. 7, no. 1, 7653. https://doi.org/10.1038/s41598-017-07923-0
Desai HR, Sivasubramaniyam T, Revelo XS, Schroer SA, Luk CT, Rikkala PR et al. Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. Scientific Reports. 2017 Dec 1;7(1). 7653. https://doi.org/10.1038/s41598-017-07923-0
Desai, Harsh R. ; Sivasubramaniyam, Tharini ; Revelo, Xavier S. ; Schroer, Stephanie A. ; Luk, Cynthia T. ; Rikkala, Prashanth R. ; Metherel, Adam H. ; Dodington, David W. ; Park, Yoo Jin ; Kim, Min Jeong ; Rapps, Joshua A. ; Besla, Rickvinder ; Robbins, Clinton S. ; Wagner, Kay Uwe ; Bazinet, Richard P. ; Winer, Daniel A. ; Woo, Minna. / Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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