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Hepcidin and Iron Homeostasis in Patients with Subacute Thyroiditis and Healthy Subjects.

ABSTRACT: Purpose:Hepcidin is an acute-phase protein involved also in regulation of iron homeostasis. The aim of the study was to prospectively assess for the first time the hepcidinEL concentration in patients with subacute thyroiditis (SAT), to identify biochemical determinants of hepcidinEL concentration and evaluate the potential role of hepcidin in SAT diagnosis and monitoring. Methods:Out of 40 patients with SAT initially recruited, restrictive inclusion criteria fulfilled 21 subjects aged 45 ± 10 years and 21 healthy control subjects (CS). HepcidinEL concentration, thyroid status, and iron homeostasis were evaluated at SAT diagnosis and following therapy and compared with CS. Results:The median hepcidinEL concentration at SAT diagnosis is higher than that in CS (48.8 (15.9-74.5) ng/mL vs. 18.2 (10.2-23.3) ng/mL, p = 0.009) and is significantly lower after treatment (4.0 (1.2-10.0) ng/mL, p = 0.007) compared with CS. The ROC analysis for hepcidinEL at SAT diagnosis revealed that area under the curve (AUC) is 0.735 (p = 0.009), and the cut-off for hepcidinEL concentration is 48.8?ng/mL (sensitivity 0.52 and specificity 0.95). HepcidinEL in SAT patients correlated with CRP (r = 0.614, p = 0.003), ferritin (r = 0.815, p < 0.001), and aTPO (r?=?-0.491, p = 0.024). On multiple regression, the correlation between hepcidinEL and ferritin was confirmed (p < 0.001). Conclusions:SAT is accompanied by a significant increase in hepcidin, which reflects an acute-phase inflammatory process. Parameters of iron homeostasis improved significantly while inflammatory indices got lower following recovery. The potential role of hepcidin as a predictive factor of the risk of SAT relapse needs to be assessed in studies on larger groups of SAT patients.

SUBMITTER: Hernik A

PROVIDER: S-EPMC6415316 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hepcidin and Iron Homeostasis in Patients with Subacute Thyroiditis and Healthy Subjects.

Hernik Aleksandra A Szczepanek-Parulska Ewelina E Filipowicz Dorota D Czarnywojtek Agata A Wrotkowska Elżbieta E Kramer Lucyna L Urbanovych Alina A Ruchała Marek M

Mediators of inflammation 20190227

<h4>Purpose</h4>Hepcidin is an acute-phase protein involved also in regulation of iron homeostasis. The aim of the study was to prospectively assess for the first time the hepcidin<sub>EL</sub> concentration in patients with subacute thyroiditis (SAT), to identify biochemical determinants of hepcidin<sub>EL</sub> concentration and evaluate the potential role of hepcidin in SAT diagnosis and monitoring.<h4>Methods</h4>Out of 40 patients with SAT initially recruited, restrictive inclusion criteria ...[more]

PMID: 30936776

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Project description:Background & aimsHepatic gluconeogenesis provides fuel during starvation, and is abnormally induced in obese individuals or those with diabetes. Common metabolic disorders associated with active gluconeogenesis and insulin resistance (obesity, metabolic syndrome, diabetes, and nonalcoholic fatty liver disease) have been associated with alterations in iron homeostasis that disrupt insulin sensitivity and promote disease progression. We investigated whether gluconeogenic signals directly control Hepcidin, an important regulator of iron homeostasis, in starving mice (a model of persistently activated gluconeogenesis and insulin resistance).MethodsWe investigated hepatic regulation of Hepcidin expression in C57BL/6Crl, 129S2/SvPas, BALB/c, and Creb3l3-/- null mice. Mice were fed a standard, iron-balanced chow diet or an iron-deficient diet for 9 days before death, or for 7 days before a 24- to 48-hour starvation period; liver and spleen tissues then were collected and analyzed by quantitative reverse-transcription polymerase chain reaction and immunoblot analyses. Serum levels of iron, hemoglobin, Hepcidin, and glucose also were measured. We analyzed human hepatoma (HepG2) cells and mouse primary hepatocytes to study transcriptional control of Hamp (the gene that encodes Hepcidin) in response to gluconeogenic stimuli using small interfering RNA, luciferase promoter, and chromatin immunoprecipitation analyses.ResultsStarvation led to increased transcription of the gene that encodes phosphoenolpyruvate carboxykinase 1 (a protein involved in gluconeogenesis) in livers of mice, increased levels of Hepcidin, and degradation of Ferroportin, compared with nonstarved mice. These changes resulted in hypoferremia and iron retention in liver tissue. Livers of starved mice also had increased levels of Ppargc1a mRNA and Creb3l3 mRNA, which encode a transcriptional co-activator involved in energy metabolism and a liver-specific transcription factor, respectively. Glucagon and a cyclic adenosine monophosphate analog increased promoter activity and transcription of Hamp in cultured liver cells; levels of Hamp were reduced after administration of small interfering RNAs against Ppargc1a and Creb3l3. PPARGC1A and CREB3L3 bound the Hamp promoter to activate its transcription in response to a cyclic adenosine monophosphate analog. Creb3l3-/- mice did not up-regulate Hamp or become hypoferremic during starvation.ConclusionsWe identified a link between glucose and iron homeostasis, showing that Hepcidin is a gluconeogenic sensor in mice during starvation. This response is involved in hepatic metabolic adaptation to increased energy demands; it preserves tissue iron for vital activities during food withdrawal, but can cause excessive iron retention and hypoferremia in disorders with persistently activated gluconeogenesis and insulin resistance.

Dataset Information

Hepcidin and Iron Homeostasis in Patients with Subacute Thyroiditis and Healthy Subjects.

Publications

Hepcidin and Iron Homeostasis in Patients with Subacute Thyroiditis and Healthy Subjects.

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