scholarly journals Bone marrow macrophage‐derived exosomal miR‐143‐5p contributes to insulin resistance in hepatocytes by repressing MKP5

2021 ◽  
Author(s):  
Linfang Li ◽  
Huiyan Zuo ◽  
Xiuqing Huang ◽  
Tao Shen ◽  
Weiqing Tang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Bone Marrow Macrophage

Fluoride modulates formation and function of bone marrow macrophage-derived osteoclasts in a strain-specific manner

2016 ◽  
Author(s):  
Oliveira Flavia Amadeu de ◽  
Pereira Amanda Amaral ◽  
Silva Ventura Talita da ◽  
Buzalaf Marilia Afonso Rabelo ◽  
Oliveira Rodrigo Cardoso de ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Macrophage ◽  
Specific Manner ◽  
And Function

CD4+ T-cell activation of bone marrow causes bone fragility and insulin resistance in type 2 diabetes

Bone ◽  
2021 ◽  
pp. 116292
Author(s):  
S.E. Cifuentes-Mendiola ◽  
D.L. Solis-Suarez ◽  
A. Martínez-Dávalos ◽  
M. Godínez-Victoria ◽  
A.L. García-Hernández
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Bone Fragility ◽  
Cd4 T Cell

scholarly journals Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis

2016 ◽  
Vol 310 (11) ◽  
pp. H1423-H1438 ◽  
Author(s):  
Petra Haberzettl ◽  
James P. McCracken ◽  
Aruni Bhatnagar ◽  
Daniel J. Conklin
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Particulate Matter ◽  
Insulin Sensitivity ◽  
Ambient Air ◽  
Air Pollutant ◽  
Ambient Air Pollution ◽  
Endothelial Progenitor ◽  
Insulin Sensitizer ◽  
Circulating Levels

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1+/Sca-1+ cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/particulate-matter-induced-vascular-insulin-resistance/ .

scholarly journals Vasodilator-stimulated phosphoprotein protects against vascular inflammation and insulin resistance

2014 ◽  
Vol 307 (7) ◽  
pp. E571-E579 ◽  
Author(s):  
Andrew M. Cheng ◽  
Norma Rizzo-DeLeon ◽  
Carole L. Wilson ◽  
Woo Je Lee ◽  
Sanshiro Tateya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Insulin Sensitivity ◽  
Vascular Tissue ◽  
Vascular Inflammation ◽  
Physiological Role ◽  
Whole Body ◽  
Aortic Tissue ◽  
Protective Effects ◽  
Downstream Mediator

Among the pleotropic effects of endothelial nitric oxide (NO) is protection against vascular inflammation during high-fat diet (HFD) feeding. The current work investigated the role of the enzyme vasodilatory-stimulated phosphoprotein (VASP) as a downstream mediator of the anti-inflammatory effect of NO signaling in vascular tissue. Relative to mice fed a low-fat diet (LFD), levels of VASP Ser239 phosphorylation, a marker of VASP activation, were dramatically reduced in aortic tissue of mice with obesity induced by consuming a HFD. As reported previously, the effect of the HFD was associated with increased aortic inflammation, as measured by increased NF-κB-dependent gene expression, and reduced vascular insulin sensitivity (including insulin-stimulated phosphorylation of eNOS and Akt). These effects of the HFD were recapitulated by VASP knockout, implying a physiological role for VASP to constrain inflammatory signaling and thereby maintain vascular insulin sensitivity. Conversely, overexpression of VASP in endothelial cells blocked inflammation and insulin resistance induced by palmitate. The finding that transplantation of bone marrow from VASP-deficient donors into normal recipients does not recapitulate the vascular effects of whole body VASP deficiency suggests that the protective effects of this enzyme are not mediated in immune or other bone marrow-derived cells. These studies implicate VASP as a downstream mediator of the NO/cGMP pathway that is both necessary and sufficient to protect against vascular inflammation and insulin resistance. As such, this work identifies VASP as a potential therapeutic target in the treatment of obesity-related vascular dysfunction.

Immunophenotypic and Morphometric Evaluation of Bone Marrow Macrophage Culture Stimulated by Sodium Aminodihydrophthalazinedione In Vitro

2021 ◽  
Vol 15 (6) ◽  
pp. 594-603
Author(s):  
V. A. Pozdina ◽  
U. V. Zvedeninova ◽  
M. V. Ulitko ◽  
I. G. Danilova ◽  
M. T. Abidov
Keyword(s):  
Bone Marrow ◽  
Macrophage Culture ◽  
Bone Marrow Macrophage ◽  
Morphometric Evaluation

scholarly journals Hematopoietic Cell–Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance

2020 ◽  
Vol 40 (3) ◽  
pp. 670-681
Author(s):  
Brian P. Dick ◽  
Ryan McMahan ◽  
Taft Knowles ◽  
Lev Becker ◽  
Sina A. Gharib ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Bone Marrow ◽  
Inflammatory Responses ◽  
Hepatic Insulin Resistance ◽  
Metabolic Homeostasis ◽  
Wild Type ◽  
Bone Marrow Derived Cells ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Objective: Mice genetically deficient in endothelial nitric oxide synthase (Nos3 −/− ) have fasting hyperinsulinemia and hepatic insulin resistance, indicating the importance of Nos3 (nitric oxide synthase) in maintaining metabolic homeostasis. Although the current paradigm holds that these metabolic effects are derived specifically from the expression of Nos3 in the endothelium, it has been established that bone marrow–derived cells also express Nos3. The aim of this study was to investigate whether bone marrow–derived cell Nos3 is important in maintaining metabolic homeostasis. Approach and Results: To test the hypothesis that bone marrow–derived cell Nos3 contributes to metabolic homeostasis, we generated chimeric male mice deficient or competent for Nos3 expression in circulating blood cells. These mice were placed on a low-fat diet for 5 weeks, a time period which is known to induce hepatic insulin resistance in global Nos3-deficient mice but not in wild-type C57Bl/6 mice. Surprisingly, we found that the absence of Nos3 in the bone marrow–derived component is associated with hepatic insulin resistance and that restoration of Nos3 in the bone marrow–derived component in global Nos3-deficient mice is sufficient to restore hepatic insulin sensitivity. Furthermore, we found that overexpression of Nos3 in bone marrow–derived component in wild-type mice attenuates the development of hepatic insulin resistance during high-fat feeding. Finally, compared with wild-type macrophages, the loss of macrophage Nos3 is associated with increased inflammatory responses to lipopolysaccharides and reduced anti-inflammatory responses to IL-4, a macrophage phenotype associated with the development of hepatic and systemic insulin resistance. Conclusions: These results would suggest that the metabolic and hepatic consequences of high-fat feeding are mediated by loss of Nos3/nitric oxide actions in bone marrow–derived cells, not in endothelial cells.

Relationships between plasma adiponectin and blood cells, hepatopancreatic enzymes in women

2004 ◽  
Vol 91 (02) ◽  
pp. 360-366 ◽  
Author(s):  
Katsuhiko Namioka ◽  
Shinji Katayose ◽  
Miyao Matsubara
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Bone Marrow ◽  
Blood Cells ◽  
White Blood Cells ◽  
Serum Triglyceride ◽  
Plasma Adiponectin ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Bone Marrow Function

SummaryAdiponectin, which is secreted specifically from adipocyte, is thought to play a key role in the metabolic syndrome. We studied the associations of plasma adiponectin concentrations with blood cells and hepatopancreatic enzymes in 339 women aged 54.0 ± 0.8 (mean ± SE) years. Plasma adiponectin before and after adjustment for body composition or calculated insulin resistance increased in slight anemic women (372.6 ± 2.6 ×104/mm3) compared with non-anemic subjects (471.1 ± 1.7) (all p < 0.0001), and were inversely associated with red blood cells (RBC), hemoglobin, hematocrit, white blood cells and platelet values (p < 0.0001 ∼ 0.02), independent of age, diastolic blood pressure, body mass index, serum triglyceride, insulin resistance or blood urea nitrogen. Age and adiponectin/body fat mass (%) were negative, and blood pressure and insulin resistance were positive significant independent determinants of RBC in stepwise regression analysis. Moreover, adiponectin before and after adjustment were inversely associated with serum ALAT,γGTP and ChE, and positively with amylase levels (p < 0.0001 ∼ 0.02). These results indicate the possibility that increased adiponectin may contribute to the suppressive bone marrow function in vivo. Combined with the leptin’s data, adipocyte derived proteins were related to the hematopoiesis, therefore it has shown the possible existence of adipose tissue/ bone marrow function linkage more clearly. Furthermore, hepatopancreatic enzyme associations with this protein may indicate the possibility that adiponectin will regulate the hepatopancreatic function in health and disease.

Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal TRIM8 as a mediator of IFN-γ hyper-responsiveness and risk for macrophage activation syndrome

2020 ◽  
pp. annrheumdis-2020-217470
Author(s):  
Grant S Schulert ◽  
Alex V Pickering ◽  
Thuy Do ◽  
Sanjeev Dhakal ◽  
Ndate Fall ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Rna Seq ◽  
Bone Marrow Macrophage ◽  
Ifn Γ ◽  
Activation Syndrome

ObjectivesSystemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening cytokine storm driven by interferon (IFN)-γ. SJIA monocytes display IFN-γ hyper-responsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte and bone marrow macrophage (BMM) polarisation phenotypes in SJIA including molecular features contributing to IFN response.MethodsBulk RNA-seq was performed on peripheral blood monocytes (n=26 SJIA patients) and single cell (sc) RNA-seq was performed on BMM (n=1). Cultured macrophages were used to define consequences of tripartite motif containing 8 (TRIM8) knockdown on IFN-γ signalling.ResultsBulk RNA-seq of SJIA monocytes revealed marked transcriptional changes in patients with elevated ferritin levels. We identified substantial overlap with multiple polarisation states but little evidence of IFN-induced signature. Interestingly, among the most highly upregulated genes was TRIM8, a positive regulator of IFN-γ signalling. In contrast to PBMC from SJIA patients without MAS, scRNA-seq of BMM from a patient with SJIA and MAS identified distinct subpopulations of BMM with altered transcriptomes, including upregulated IFN-γ response pathways. These BMM also showed significantly increased expression of TRIM8. In vitro knockdown of TRIM8 in macrophages significantly reduced IFN-γ responsiveness.ConclusionsMacrophages with an ‘IFN-γ response’ phenotype and TRIM8 overexpression were expanded in the bone marrow from an MAS patient. TRIM8 is also upregulated in SJIA monocytes, and augments macrophage IFN-γ response in vitro, providing both a candidate molecular mechanism and potential therapeutic target for monocyte hyper-responsiveness to IFNγ in cytokine storms including MAS.

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