Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1422-1433 |
| Number of pages | 12 |
| Journal | Immunity |
| Volume | 44 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2016 Jun 21 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology
Cite this
Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation. / Masamoto, Yosuke; Arai, Shunya; Sato, Tomohiko; Yoshimi, Akihide; Kubota, Naoto; Takamoto, Iseki; Iwakura, Yoichiro; Yoshimura, Akihiko; Kadowaki, Takashi; Kurokawa, Mineo.
In: Immunity, Vol. 44, No. 6, 21.06.2016, p. 1422-1433.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84975049803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975049803&partnerID=8YFLogxK
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 -