scholarly journals Hepcidin Expression in Adipose Tissue Increases during Cardiac Surgery

2010 ◽  
pp. 393-400 ◽  
Author(s):  
M Vokurka ◽  
Z Lacinová ◽  
J Křemen ◽  
P Kopecký ◽  
J Bláha ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Iron Metabolism ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Phase Reaction ◽  
Anemia Of Chronic Disease ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Hepcidin Expression ◽  
Massive Obesity

Hepcidin, a key regulator of iron metabolism, plays a crucial role in the pathogenesis of anemia of chronic disease. Although it is produced mainly in the liver, its recently described expression in adipose tissue has been shown to be enhanced in massive obesity due to chronic low-grade inflammation. Our objective was to study the changes in hepcidin expression in adipose tissue during acute-phase reaction. We measured hepcidin mRNA expression from isolated subcutaneous and epicardial adipose tissue at the beginning and at the end of the surgery. The expression of mRNAs for hepcidin and other iron-related genes (transferrin receptor 1, divalent metal transporter 1, ferritin, ferroportin) were measured by real-time RT-PCR. Hepcidin expression significantly increased at the end of the surgery in subcutaneous but not in epicardial adipose tissue. Apart from the increased levels of cytokines, the parameters of iron metabolism showed typical inflammation-induced changes. We suggest that acute inflammatory changes could affect the regulation of hepcidin expression in subcutaneous adipose tissue and thus possibly contribute to inflammation-induced systemic changes of iron metabolism.

The Role of Epicardial Adipose Tissue Lymphocytes in Low-Grade Inflammation and Coronary Artery Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 469-P
Author(s):  
MILOS MRAZ ◽  
ANNA CINKAJZLOVA ◽  
ZDENA LACINOVÁ ◽  
JANA KLOUCKOVA ◽  
HELENA KRATOCHVILOVA ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Artery Disease ◽  
Low Grade Inflammation

scholarly journals Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Miloš Mráz ◽  
Anna Cinkajzlová ◽  
Jana Kloučková ◽  
Zdeňka Lacinová ◽  
Helena Kratochvílová ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Dendritic Cells ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Epicardial Adipose Tissue ◽  
Low Grade ◽  
Elective Cardiac Surgery ◽  
Artery Disease

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n=12) and without (non-T2DM, n=17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6±0.7 vs. 5.8±0.2 mmol/l, p<0.001) and glycated hemoglobin (52.0±3.4 vs. 36.9±1.0 mmol/mol, p<0.001) and tended to have more pronounced inflammation (hsCRP: 9.8±3.1 vs. 5.1±1.9 mg/ml, p=0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57±0.65 vs. 4.45±1.56% for T2DM vs. non-T2DM, p=0.041) with a similar, albeit insignificant, trend in EAT (0.996±0.33 vs. 2.46±0.78% for T2DM vs. non-T2DM, p=0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5±2.0 vs. 4.6±1.9% of DC cells, p=0.005) and EAT (29.1±8.7 vs. 8.4±2.4% of DC, p=0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1±8.7 vs. 13.5±2.0% of DC, p=0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

Relationship between intestinal iron-transporter expression, hepatic hepcidin levels and the control of iron absorption

2002 ◽  
Vol 30 (4) ◽  
pp. 724-726 ◽  
Author(s):  
G.J. Anderson ◽  
D. M. Frazer ◽  
S.J. Wilkins ◽  
E. M. Becker ◽  
K. N. Millard ◽  
...  
Keyword(s):  
Iron Transport ◽  
Iron Absorption ◽  
Negative Regulator ◽  
Deficient Diet ◽  
Divalent Metal Transporter 1 ◽  
Intestinal Iron Absorption ◽  
Divalent Metal Transporter ◽  
Hepcidin Expression ◽  
Iron Deficient ◽  
Transport Molecules

Hepcidin is an anti-microbial peptide predicted to be involved in the regulation of intestinal iron absorption. We have examined the relationship between the expression of hepcidin in the liver and the expression of the iron-transport molecules divalent-metal transporter 1, duodenal cytochrome b, hephaestin and Ireg1 in the duodenum of rats switched from an iron-replete to an iron-deficient diet or treated to induce an acute phase response. In each case, elevated hepcidin expression correlated with reduced iron absorption and depressed levels of iron-transport molecules. These data are consistent with hepcidin playing a role as a negative regulator of intestinal iron absorption.

scholarly journals Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Weigang Shu ◽  
Zhi Pang ◽  
Chunjin Xu ◽  
Jian Lin ◽  
Gengfeng Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Iron Metabolism ◽  
Bowel Disease ◽  
Caspase 3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anemia Of Chronic Disease ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Inflammatory Bowel

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn’s disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

scholarly journals EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Dan Chen ◽  
Anumantha G. Kanthasamy ◽  
Manju B. Reddy
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Regulatory Gene ◽  
Cell Uptake ◽  
Dopamine Depletion ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Sytox Green ◽  
Gene And Protein Expression

Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression.Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells.Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry.Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05) increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased55Fe (by 96%,p<0.01) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001) TH+cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons.Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.

scholarly journals Effects of acute and chronic inflammation on proteins involved in duodenal iron absorption in mice: a time-course study

2012 ◽  
Vol 108 (11) ◽  
pp. 1994-2001 ◽  
Author(s):  
Abitha Sukumaran ◽  
Joe Varghese ◽  
Jesintha Tamilselvan ◽  
Visalakshi Jeyaseelan ◽  
Thenmozhi Mani ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Early Time ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Expression Levels ◽  
Hepcidin Expression ◽  
Time Course Study ◽  
Acute And Chronic Inflammation

In order to understand better the molecular mechanisms involved in the pathogenesis of anaemia of inflammation, we carried out a time-course study on the effects of turpentine-induced acute and chronic inflammation on duodenal proteins involved in Fe absorption in mice. Expression levels of these proteins and hepatic hepcidin and serum Fe levels were determined in inflamed mice. In acutely inflamed mice, significantly increased expression of ferritin was the earliest change observed, followed by decreased divalent metal transporter 1 expression in the duodenum and increased hepcidin expression in the liver. Ferroportin expression increased subsequently, despite high levels of hepcidin. Hypoferraemia, which developed at early time periods studied, was followed by increased serum Fe levels at later points. The present results thus show that acute inflammation induced several changes in the expression of proteins involved in duodenal Fe absorption, contributing to the development of hypoferraemia. Resolution of inflammation caused attenuation of many of these effects. Effects in chronically inflamed mice were less consistent. The present results also suggest that inflammation-induced increases in ferritin appeared to override the effects of hepcidin on the expression levels of ferroportin in enterocytes.

scholarly journals Small molecule inhibitors of divalent metal transporter-1

2009 ◽  
Vol 296 (4) ◽  
pp. G798-G804 ◽  
Author(s):  
Peter D. Buckett ◽  
Marianne Wessling-Resnick
Keyword(s):  
Small Molecule ◽  
Iron Metabolism ◽  
Iron Uptake ◽  
Small Molecule Inhibitors ◽  
Structural Features ◽  
Divalent Metal ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Copper Chelation ◽  
Metal Transporter

Divalent metal transporter-1 (DMT1) is a divalent cation transporter that plays a key role in iron metabolism by mediating ferrous iron uptake across the small intestine. We have previously identified several small molecule inhibitors of iron uptake ( 4 ). Using a cell line that stably overexpresses DMT1, we screened the ability of these inhibitors to specifically block this transporter's activity. One compound, NSC306711, inhibited DMT1-mediated iron uptake in a reversible and competitive manner. This inhibitor is a polysulfonated dye containing two copper centers. Although one of these two sites could be chelated by Triethylenetetramine copper chelation did not perturb NSC306711 inhibition of DMT1 activity. Several other polysulfonated dyes with structural features similar to NSC306711 were identified as potential DMT1 transport inhibitors. This study characterizes important pharmacological tools that can be used to probe DMT1's mechanism of iron transport and its role in iron metabolism.

scholarly journals Decreased hepatic iron in response to alcohol may contribute to alcohol-induced suppression of hepcidin

2016 ◽  
Vol 115 (11) ◽  
pp. 1978-1986 ◽  
Author(s):  
Joe Varghese ◽  
Jithu Varghese James ◽  
Sreerohini Sagi ◽  
Subhosmito Chakraborty ◽  
Abitha Sukumaran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Time Course ◽  
Histopathological Examination ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Hepcidin Expression ◽  
Cytochrome P4502e1 ◽  
Metal Transporter ◽  
Serum Hepcidin ◽  
Time Course Study

AbstractHepatic Fe overload has often been reported in patients with advanced alcoholic liver disease. However, it is not known clearly whether it is the effect of alcohol that is responsible for such overload. To address this lacuna, a time-course study was carried out in mice in order to determine the effect of alcohol on Fe homoeostasis. Male Swiss albino mice were pair-fed Lieber–DeCarli alcohol diet (20 % of total energy provided as alcohol) for 2, 4, 8 or 12 weeks. Expression levels of duodenal and hepatic Fe-related proteins were determined by quantitative PCR and Western blotting, as were Fe levels and parameters of oxidative stress in the liver. Alcohol induced cytochrome P4502E1 and oxidative stress in the liver. Hepatic Fe levels and ferritin protein expression dropped to significantly lower levels after 12 weeks of alcohol feeding, with no significant effects at earlier time points. This was associated, at 12 weeks, with significantly decreased liver hepcidin expression and serum hepcidin levels. Protein expressions of duodenal ferroportin (at 8 and 12 weeks) and divalent metal transporter 1 (at 8 weeks) were increased. Serum Fe levels rose progressively to significantly higher levels at 12 weeks. Histopathological examination of the liver showed mild steatosis, but no stainable Fe in mice fed alcohol for up to 12 weeks. In summary, alcohol ingestion by mice in this study affected several Fe-related parameters, but produced no hepatic Fe accumulation. On the contrary, alcohol-induced decreases in hepatic Fe levels were seen and may contribute to alcohol-induced suppression of hepcidin.

scholarly journals Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
J. C. Fernandes ◽  
P. Garrido ◽  
S. Ribeiro ◽  
P. Rocha-Pereira ◽  
E. Bronze-da-Rocha ◽  
...  
Keyword(s):  
Serum Iron ◽  
Rare Complication ◽  
Therapeutic Strategies ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Hepcidin Expression ◽  
Metal Transporter ◽  
Human Erythropoietin ◽  
Underlying Mechanisms ◽  
The Impact

Erythroid hypoplasia (EH) is a rare complication associated with recombinant human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified. Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver. DecreasedEPOexpression was observed in kidney and liver, while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis. These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy.

Iron metabolism in obese children and adolescents

2021 ◽  
Vol 11 (1) ◽  
pp. 44-49
Author(s):  
N.N. Smirnova ◽  
◽  
N.B. Kuprienko ◽  
V.P. Novikova ◽  
A.I. Khavkin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Iron Metabolism ◽  
Iron Deficiency Anaemia ◽  
Molecular Mechanisms ◽  
Key Words Children ◽  
Low Grade ◽  
Obese Children ◽  
Deficiency Anaemia ◽  
Low Grade Inflammation ◽  
Excessive Accumulation

The review presents new data about the causes and molecular mechanisms of iron metabolism in obesity. Obesity is associated with dysregulated iron metabolism. Three hypotheses of the hypoferremia of obesity have been proposed: nutrition hypothesis, large blood volume hypothesis, and the inflammation hypothesis. The latter has been better supported, it is consistent with the data about low-grade inflammation taking place in excessive accumulation of adipose tissue. The key role in the development of functional hypoferremia belongs to the hepcidin-leptin association. Key words: children, iron deficiency anaemia, iron metabolism, obesity, adolescents

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