Hepcidin Expression in Adipose Tissue Increases during Cardiac
Surgery

Vokurka, Martin; Lacinová, Z; Kremen, J; Kopecký, P; Bláha, J; Pelinková, Květa; Haluzík, M; Nečas, E

doi:10.33549/physiolres.931759

Cited by 21 publications

(1 citation statement)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inflammatory changes of hepcidin are supposed to control iron availability for microorganisms during the infection, however they contribute to iron-restricted erythropoiesis in anemia of chronic disease (Weiss and Goodnough 2005). Different research groups discovered that IL-6, through the Jak/STAT-3 signaling pathway, is involved in regulation of hepcidin levels in response to inflammatory stimuli (Wrighting andAndrews 2006, Truksa et al 2007). Considering a dominant regulation by IL-6, hepcidin was classified as a type II acute-phase protein (Nemeth et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Plasma Hepcidin Correlates Positively With Interleukin-6 in Patients Undergoing Pulmonary Endarterectomy

Maruna

Vokurka²,

Lindner³

2011

Physiol Res

View full text Add to dashboard Cite

Hepcidin, a recently discovered antimicrobial peptide synthesized in the liver, was identified to be the key mediator of iron metabolism and distribution. Despite our knowledge of hepcidin increased in recent years, there are only limited data on hepcidin regulation during systemic inflammatory response in human subjects. In a prospective study, the time course of plasma hepcidin was analyzed in relations to six inflammatory parameters – plasma cytokines and acute-phase proteins in patients undergoing uncomplicated pulmonary endarterectomy. Twenty-four patients (males, aged 52.6±10.2 years, treated with pulmonary endarterectomy in a deep hypothermic circulatory arrest) were enrolled into study. Hepcidin, interleukin (IL)-6, IL-8, tumor necrosis factor-α, C-reactive protein, α1-antitrypsin and ceruloplasmin arterial concentrations were measured before surgery and repeatedly within 120 h post-operatively. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. In a postoperative period, hepcidin increased from preoperative level 8.9 ng/ml (6.2-10.7) (median and interquartile range) to maximum 16.4 ng/ml (14.1-18.7) measured 72 h after the end of surgery. Maximum post-operative concentrations of hepcidin correlated positively with maximum IL-6 levels. Both hepcidin and IL-6 maximum concentrations correlated positively with extracorporeal circulation time. In conclusions, the study demonstrated that plasma hepcidin is a positive acute-phase reactant in relation to an uncomplicated large cardiac surgery. Hepcidin increase was related to IL-6 concentrations and to the duration of surgical procedure. Our clinical findings are in conformity with recent experimental studies defining hepcidin as a type II acute-phase protein.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasma Hepcidin Correlates Positively With Interleukin-6 in Patients Undergoing Pulmonary Endarterectomy

Maruna

Vokurka²,

Lindner³

2011

Physiol Res

View full text Add to dashboard Cite

show abstract

Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and inflammatory challenge

Andrews

Arredondo

2012

Biometals

View full text Add to dashboard Cite

Adipose tissue secretes numerous pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α that can lead to insulin resistance (IR). In the liver, both IL-6 and TNF-α induce IR by inhibiting phosphorylation or ubiquitination of IRS1. In IR development, Fe is a risk factor in type-2 diabetes development. We studied the expression of genes related to inflammation, hypoxia, and mitochondrial function in hepatic (HepG2) and adipose (3T3-L1) cells. HepG2 and 3T3-L1 cells were incubated with 20 μM Fe, 40 μM Fe, or 40 μM Fe/20 mM glucose for 7 days and then challenged with 20 ng/ml IL-6 and/or 100 μM CoCl(2) for 20 h. We measured intracellular Fe levels and the relative expression of hepcidin, NF-κB, IL-6, TNF-α, hypoxia inducible factor 1α (HIF-1α), and mitofusin 2 (Mfn-2) mRNA using qRT-PCR. The intracellular Fe concentration in HepG2 cells did not change with 20 or 40 μM Fe. However, levels were decreased with Fe/glucose and IL-6 and/or CoCl(2). 3T3-L1 cells showed an increase in intracellular Fe with high Fe plus either IL-6 or CoCl(2). HepG2 cells incubated with 40 μM Fe alone or Fe/glucose and challenged with IL-6 and/or CoCl(2) showed increased IL-6, NF-κB, and TNF-α mRNA expression and decreased mRNA expression of Mfn-2 in all experimental conditions. 3T3-L1 cells incubated with 40 μM Fe alone or Fe/glucose and challenged with IL-6 showed increased NF-κB mRNA expression and decreased Mfn-2 expression in all experimental conditions. Thus, high Fe, inflammation, and hypoxia trigger the expression of genes related to inflammation and Fe metabolism in HepG2 cells, in 3T3-L1 cells the same stimuli increased NF-kB and hepcidin expression.

show abstract

Expression of genes associated with inflammation and iron metabolism in 3T3-L1 cells induced with macrophages-conditioned medium, glucose and iron

et al. 2018

View full text Add to dashboard Cite

Obesity is characterized by a chronic inflammatory process, with an increased volume of total adipose tissue, especially visceral, which secretes pro-inflammatory cytokines such as TNF-α and IL-6. Hepcidin (Hpc), a main iron metabolism regulator, is synthetized by an IL-6 stimuli, among others, in liver and adipose tissue, favoring an association between the inflammatory process and iron metabolism. Still there are questions remain regarding the interaction of these factors. Our aim was to study the effect of a macrophage-conditioned medium (MCM) on adipocyte cells challenged with glucose and/or iron. We studied the mRNA relative abundance of genes related to inflammation in differentiated 3T3-L1 cells challenged with Fe (40 µM), glucose (20 mM) or Fe/glucose (40 µM/20 mM) with or without MCM for 24 h. We also measured the intracellular iron levels under these conditions. Our results showed that when adipocytes were challenged with MCM, glucose and/or Fe, the intracellular iron and mRNA levels of pro-inflammatory cytokines increased. These responses were higher when all the stimuli were combined with MCM from macrophages. Thus, we showed that combined high glucose/high Fe alone or with MCM may contribute to an increase on intracellular iron and inflammatory response in 3T3-L1 differentiated cells, by increased mRNA levels of IL-6, TNF-α, MCP-1, Hpc and reducing adiponectin levels, enhancing the inflammatory processes.

show abstract

Hepcidin Expression in Adipose Tissue Increases during Cardiac Surgery

Cited by 21 publications

References 40 publications

Plasma Hepcidin Correlates Positively With Interleukin-6 in Patients Undergoing Pulmonary Endarterectomy

Plasma Hepcidin Correlates Positively With Interleukin-6 in Patients Undergoing Pulmonary Endarterectomy

Hepatic and adipocyte cells respond differentially to iron overload, hypoxic and inflammatory challenge

Expression of genes associated with inflammation and iron metabolism in 3T3-L1 cells induced with macrophages-conditioned medium, glucose and iron

Contact Info

Product

Resources

About