scholarly journals M2 macrophage-secreted Slit3 intensifies sympathetic nerve function in adipose tissue and enhances thermogenesis: A long-term cold adaption way

2021 ◽  
Author(s):  
Yina Wang ◽  
Yan Tang ◽  
Zhihui He ◽  
Hong Ma ◽  
Jiashen Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Sympathetic Nerve ◽  
Underlying Mechanism ◽  
Sympathetic Neuron ◽  
M2 Macrophage ◽  
Nerve Function ◽  
M2 Macrophages ◽  
Cold Adaption ◽  
Macrophage Cytokine

Abstract Beiging of white adipose tissue (WAT) is capable of adaptive thermogenesis and dissipating energy. The beiging processes have been associated with the increase of anti-inflammatory M2 macrophages, however the function of M2 macrophage on beiging and the underlying mechanism are not fully understood. Here we identified a macrophage cytokine Slit3 by analyzing the transcriptome of M2 macrophages collected with FACS in inguinal WAT (iWAT) of mice after cold exposure. Once released from macrophages, Slit3 bound to the ROBO1 receptor on sympathetic neuron and activated tyrosine hydrolase (TH) through PKA and CaMKⅡ signaling, and thus stimulated norepinephrine (NE) synthesis and release. NE acts on adipocytes and stimulate thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT depot acquired local adipocytes with beiging phenotype and enhanced thermogenesis. In addition, mice bearing the myeloid inactivation of Slit3 were cold intolerant and gained more weight due to the lowered metabolic rate. Collectively, we demonstrate Slit3 is a macrophage cytokine and promotes beiging and thermogenesis through intensifying the sympathetic nerve function. As the expanded M2 macrophages are integral cell population in adipose tissue, the macrophage-Slit3-sympathetic neuron-adipocyte axis assures the long-term cold adaption.

scholarly journals Targeted Deletion of Adipocytes by Apoptosis Leads to Adipose Tissue Recruitment of Alternatively Activated M2 Macrophages

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3074-3081 ◽  
Author(s):  
Pamela Fischer-Posovszky ◽  
Qiong A. Wang ◽  
Ingrid Wernstedt Asterholm ◽  
Joseph M. Rutkowski ◽  
Philipp E. Scherer
Keyword(s):  
Adipose Tissue ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Proinflammatory Response ◽  
Targeted Deletion ◽  
Fat Depots ◽  
Inflammatory Status ◽  
Polychromatic Flow Cytometry ◽  
M1 Phenotype ◽  
Alternatively Activated

Obesity is frequently associated with an infiltration of macrophages into adipose tissue. Adipocyte dysfunction causes a phenotypic switch of macrophages from an alternatively activated M2-like phenotype towards a proinflammatory M1 phenotype. The cross talk between adipocytes and infiltrating immune cells, in particular macrophages, is thought to contribute to local and eventually systemic inflammation. Here, we tested the phenotypic impact of a lack of adipocytes on the inflammatory status of macrophages. We took advantage of the fat apoptosis through targeted activation of caspase-8 (FAT-ATTAC) mouse model that allows for the inducible system-wide elimination of adipocytes through a proapoptotic mechanism and followed the degree and type of inflammatory response upon ablation of live adipocytes. Analysis of depots 2 wk after elimination of adipocytes resulted in markedly reduced levels of adipose tissue and a robust down-regulation of circulating adipokines. Quantitative PCR and immunohistochemistry on epididymal and inguinal fat depots revealed an increase of the macrophage markers F4/80 and CD11c. Using polychromatic flow cytometry, we observed an up-regulation of alternatively activated M2 macrophage markers (CD206 and CD301) on the majority of F4/80 positive cells. Apoptosis of adipocytes is sufficient to initiate a large influx of macrophages into the remnant fat pads. However, these macrophages are alternatively activated, antiinflammatory M2 macrophages and not M1 cells. We conclude that adipocyte death is sufficient to initiate macrophage infiltration, and live adipocytes are required to initiate and/or sustain a proinflammatory response within the infiltrating macrophages in adipose tissue.

scholarly journals ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Dafeng Xu ◽  
Yu Wang ◽  
Jincai Wu ◽  
Zhensheng Zhang ◽  
Jiacheng Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Aerobic Glycolysis ◽  
Macrophage Polarization ◽  
Underlying Mechanism ◽  
Integrated Analysis ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Tumor Associated Macrophages ◽  
In Vivo Experiments

AbstractHepatocellular carcinoma (HCC) is a common high-mortality cancer, mainly due to diagnostic difficulties during its early clinical stages. In this study, we aimed to identify genes that are important for HCC diagnosis and treatment, and we investigated the underlying mechanism of prognostic differences. Differentially expressed genes (DEGs) were identified by using the limma package, and receiver operating characteristic curve analysis was performed to identify diagnostic markers for HCC. Bioinformatics and clinical specimens were used to assess epithelial cell transforming 2 (ECT2) in terms of expression, prognostic value, pathways, and immune correlations. In vitro experiments were used to investigate the underlying mechanism and function of ECT2, and the results were confirmed through in vivo experiments. The integrated analysis revealed 53 upregulated DEGs, and one candidate biomarker for diagnosis (ECT2) was detected. High expression of ECT2 was found to be an independent prognostic risk factor for HCC. ECT2 expression showed a strong correlation with tumor-associated macrophages. We found that ECT2 overexpression increased the migration and proliferation of HCC cells. It also promoted the expression of PLK1, which subsequently interacted with PTEN and interfered with its nuclear translocation, ultimately enhancing aerobic glycolysis and promoting M2 macrophage polarization. M2 macrophages suppress the functions of NK cells and T cells, and this was confirmed in the in vivo experiments. Overall, ECT2 may promote the polarization of M2 macrophages by enhancing aerobic glycolysis and suppressing the functions of immune cells. ECT2 could serve as a candidate diagnostic and prognostic biomarker for HCC.

scholarly journals Vitamin D and Macrophage Polarization in Epicardial Adipose Tissue of Atherosclerotic Swine

2018 ◽  
Author(s):  
Palanikumar Gunasekar ◽  
Vicki J. Swier ◽  
Jonathan P. Fleegel ◽  
Chandra S. Boosani ◽  
Mohamed M. Radwan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Macrophage Polarization ◽  
Coronary Intervention ◽  
Vitamin D Supplementation ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Cellular Mechanisms ◽  
Significant Difference

AbstractVitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exacerbates inflammation by increasing pro-inflammatory M1 macrophages, while vitamin D-supplementation attenuates the inflammatory cytokines and promotes M2 macrophages in EAT. This study demonstrates the significance of vitamin D mediated inhibition of macrophage mediated inflammation in the EAT during coronary intervention in addition to its immunomodulatory role. However, additional studies are required to identify the cellular mechanisms that transduce signals between macrophages and smooth muscle cells during restenosis in the presence and absence of vitamin D.Author Contribution StatementDKA conceived and designed the experiments; PG, JPF, MMR performed the experiments; PG, JPF, VJS analyzed and interpreted the results; PG prepared the figures and wrote the initial draft of the manuscript; CSB, DKA revised and edited the revised manuscript.

scholarly journals Endothelial-mesenchymal transition harnesses HSP90α-secreting M2-macrophages to exacerbate pancreatic ductal adenocarcinoma

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Chi-Shuan Fan ◽  
Li-Li Chen ◽  
Tsu-An Hsu ◽  
Chia-Chi Chen ◽  
Kee Voon Chua ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Underlying Mechanism ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Mesenchymal Transition

Abstract Background Endothelial-to-mesenchymal transition (EndoMT) can provide a source of cancer-associated fibroblasts which contribute to desmoplasia of many malignancies including pancreatic ductal adenocarcinoma (PDAC). We investigated the clinical relevance of EndoMT in PDAC, and explored its underlying mechanism and therapeutic implication. Methods Expression levels of 29 long non-coding RNAs were analyzed from the cells undergoing EndoMT, and an EndoMT index was proposed to survey its clinical associations in the PDAC patients of The Cancer Genome Atlas database. The observed clinical correlation was further confirmed by a mouse model inoculated with EndoMT cells-involved PDAC cell grafts. In vitro co-culture with EndoMT cells or treatment with the conditioned medium were performed to explore the underlying mechanism. Because secreted HSP90α was involved, anti-HSP90α antibody was evaluated for its inhibitory efficacy against the EndoMT-involved PDAC tumor. Results A combination of low expressions of LOC340340, LOC101927256, and MNX1-AS1 was used as an EndoMT index. The clinical PDAC tissues with positive EndoMT index were significantly correlated with T4-staging and showed positive for M2-macrophage index. Our mouse model and in vitro cell-culture experiments revealed that HSP90α secreted by EndoMT cells could induce macrophage M2-polarization and more HSP90α secretion to promote PDAC tumor growth. Furthermore, anti-HSP90α antibody showed a potent therapeutic efficacy against the EndoMT and M2-macrophages-involved PDAC tumor growth. Conclusions EndoMT cells can secrete HSP90α to harness HSP90α-overproducing M2-type macrophages to promote PDAC tumor growth, and such effect can be targeted and abolished by anti-HSP90α antibody.

scholarly journals Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity

2019 ◽  
Vol 20 ◽  
pp. 38-50 ◽  
Author(s):  
Marie-Therese Rached ◽  
Steven J. Millership ◽  
Silvia M.A. Pedroni ◽  
Agharul I. Choudhury ◽  
Ana S.H. Costa ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Sympathetic Nerve ◽  
Nerve Function

scholarly journals Adipose Tissue Transplant Impregnated with Collagen Increases Engraftment by Promoting Cell Proliferation, Neovascularization, and Macrophage Activity in a Rat

2021 ◽  
Author(s):  
Chika Suzuki ◽  
Takako Komiya ◽  
Hana Inoue ◽  
Takayuki Yoshimoto ◽  
Hajime Matsumura
Keyword(s):  
Cell Proliferation ◽  
Adipose Tissue ◽  
Total Cell ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Vegf Mrna ◽  
Macrophage Activity ◽  
M1 Macrophage ◽  
Adiponectin Mrna ◽  
Tissue Transplant

Abstract Objectives: To clarify the effect of impregnating transplanted adipose tissue with collagen on angiogenesis, cell proliferation, and tissue remodeling process and to reveal whether collagen impregnation contributes to improving the engraftment of transplanted adipose tissue in rats.Methods: Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi-quantitatively evaluated and underwent HE or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularization. Macrophages were evaluated using flow cytometry, and the adiponectin or VEGF mRNA was detected using real-time PCR. Results: By impregnating transplanted adipose tissue with collagen, higher engraftment rate semi-quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage, and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased.Discussion: In rats, collagen impregnation enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularization. Therefore, impregnating transplanted adipose tissue with collagen could increase the engraftment rate of adipose tissue.

Influence of adventitia injury-induced atherosclerosis on sympathetic nerve function in rabbits

2010 ◽  
Vol 30 (6) ◽  
pp. 585-589
Author(s):  
Wei CHEN ◽  
Chun LIANG ◽  
Xing LIU ◽  
Hua WANG ◽  
Wei-jian ZHOU ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Nerve Function

Long-term serial changes of cardiac sympathetic nerve dysfunction in acute decompensated heart failure patients with reduced, mid-range and preserved left ventricular ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Seo ◽  
T Yamada ◽  
T Watanabe ◽  
T Morita ◽  
Y Furukawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sympathetic Nerve ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Left Ventricular Ejection ◽  
Mibg Imaging ◽  
Cardiac Sympathetic Nerve ◽  
Heart Failure Hospitalization ◽  
Nerve Dysfunction

Abstract Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with chronic heart failure (CHF). Serial evaluation of cardiac MIBG imaging was shown to be useful for predicting adverse outcome in CHF. However, there was no information available on long-term serial changes of cardiac sympathetic nerve dysfunction after discharge of acute decompensated heart failure (ADHF) hospitalization. Purpose We aimed to clarify the serial change of cardiac MIBG imaging parameter in long-term after discharge of heart failure hospitalization, especially relating to HFrEF (LVEF<40%), HFmrEF (40%≤LVEF<50%) and HFpEF (LVEF≥50%). Methods We studied 112 patients (HFrEF; n=44, HFmrEF; n=23 and HFpEF; n=45) who were admitted for ADHF, discharged with survival and without heart failure hospitalization during follow-up period. All patients underwent cardiac MIBG imaging at the timing of discharge, in 6–12 months and in 18–24 months after discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). The cardiac MIBG washout rate (WR) was calculated from the early and delayed planar images after taking radioactive decay of I-123 into consideration. Results In HFrEF patients, late H/M was significantly improved from discharge to 6–12 months data (1.60±0.24 vs 1.75±0.31, p<0.0001). Late H/M of HFmrEF patients was also significantly improved from discharge to 18–24 months data (1.71±0.27 vs 1.84±0.29 p=0.043). On the other hand, late H/M of HFpEF patients was not significantly changed. As for WR, WR in HFrEF and HFmrEF patients was significantly improved from discharge to 18–24 months data, although WR of HFpEF was not significantly changed. Conclusion The improvement in cardiac sympathetic nerve dysfunction was observed in patients with HFrEF and HFmrEF, not in HFpEF, after the discharge of acute heart failure hospitalization. Funding Acknowledgement Type of funding source: None

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