TY - JOUR
T1 - Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation
AU - Masamoto, Yosuke
AU - Arai, Shunya
AU - Sato, Tomohiko
AU - Yoshimi, Akihide
AU - Kubota, Naoto
AU - Takamoto, Iseki
AU - Iwakura, Yoichiro
AU - Yoshimura, Akihiko
AU - Kadowaki, Takashi
AU - Kurokawa, Mineo
N1 - Funding Information:
We thank Dr. T. Kitamura for PLAT-E packaging cells; Dr. K. Nakamura, Ms. M. Yamamoto, Ms. Y. Shimamura, and Dr. J. Iino for expert technical assistance; and Kyowa Hakko Kirin Co. Ltd. for recombinant human G-CSF. This work was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. 24249055 and No. 25221305), Advanced Research & Development Programs for Medical Innovation (AMED-CREST). M.K. received lecture and advisory fee and research funding from Kyowa Hakko Kirin Co Ltd. S.A., N.K., and T.K. have also received research funding from Kyowa Hakko Kirin Co Ltd.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/21
Y1 - 2016/6/21
N2 - Obesity has been shown to increase the morbidity of infections, however, the underlying mechanisms remain largely unknown. Here we demonstrate that obesity caused adiponectin deficiency in the bone marrow (BM), which led to an inflamed BM characterized by increased tumor necrosis factor (TNF) production from bone marrow macrophages. Hematopoietic stem and progenitor cells (HSPCs) chronically exposed to excessive TNF in obese marrow aberrantly expressed cytokine signaling suppressor SOCS3, impairing JAK-STAT mediated signal transduction and cytokine-driven cell proliferation. Accordingly, both obese and adiponectin-deficient mice showed attenuated clearance of infected Listeria monocytogenes, indicating that obesity or loss of adiponectin is critical for exacerbation of infection. Adiponectin treatment restored the defective HSPC proliferation and bacterial clearance of obese and adiponectin-deficient mice, affirming the importance of adiponectin against infection. Taken together, our findings demonstrate that obesity impairs hematopoietic response against infections through a TNF-SOCS3-STAT3 axis, highlighting adiponectin as a legitimate target against obesity-related infections. Infection is a well-known complication of obesity. Kurokawa and colleagues demonstrated that adiponectin deficiency in obese bone marrow leads to inflammatory cytokine milieu characterized by high TNF and inhibits emergency granulopoiesis upon systemic bacterial infection, highlighting adiponectin as a legitimate target for obesity-related bacterial infections.
AB - Obesity has been shown to increase the morbidity of infections, however, the underlying mechanisms remain largely unknown. Here we demonstrate that obesity caused adiponectin deficiency in the bone marrow (BM), which led to an inflamed BM characterized by increased tumor necrosis factor (TNF) production from bone marrow macrophages. Hematopoietic stem and progenitor cells (HSPCs) chronically exposed to excessive TNF in obese marrow aberrantly expressed cytokine signaling suppressor SOCS3, impairing JAK-STAT mediated signal transduction and cytokine-driven cell proliferation. Accordingly, both obese and adiponectin-deficient mice showed attenuated clearance of infected Listeria monocytogenes, indicating that obesity or loss of adiponectin is critical for exacerbation of infection. Adiponectin treatment restored the defective HSPC proliferation and bacterial clearance of obese and adiponectin-deficient mice, affirming the importance of adiponectin against infection. Taken together, our findings demonstrate that obesity impairs hematopoietic response against infections through a TNF-SOCS3-STAT3 axis, highlighting adiponectin as a legitimate target against obesity-related infections. Infection is a well-known complication of obesity. Kurokawa and colleagues demonstrated that adiponectin deficiency in obese bone marrow leads to inflammatory cytokine milieu characterized by high TNF and inhibits emergency granulopoiesis upon systemic bacterial infection, highlighting adiponectin as a legitimate target for obesity-related bacterial infections.
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U2 - 10.1016/j.immuni.2016.05.010
DO - 10.1016/j.immuni.2016.05.010
M3 - Article
C2 - 27317261
AN - SCOPUS:84975049803
VL - 44
SP - 1422
EP - 1433
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -