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Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

ABSTRACT: Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Research Network (CRN). Clinical, histologic, and laboratory data were compared using nonparametric statistics and multivariate logistic regression. NAFLD patients with C282Y, but not H63D mutations, had lower median serum hepcidin levels (57 versus 65 ng/mL; P = 0.01) and higher mean hepatocellular (HC) iron grades (0.59 versus 0.28; P < 0.001), compared to wild-type (WT) subjects. Subjects with hepatic iron deposition had higher serum hepcidin levels than subjects without iron for all HFE genotypes (P < 0.0001). Hepcidin levels were highest among patients with mixed HC/reticuloendothelial system cell (RES) iron deposition. H63D mutations were associated with higher steatosis grades and NAFLD activity scores (odds ratio [OR], ?1.4; 95% confidence interval [CI]: >1.0, ?2.5; P ? 0.041), compared to WT, but not with either HC or RES iron. NAFLD patients with C282Y mutations had less ballooning or NASH (OR, ?0.62; 95% CI: >0.39, <0.94; P ? 0.024), compared to WT subjects.The presence of C282Y mutations in patients with NAFLD is associated with greater HC iron deposition and decreased serum hepcidin levels, and there is a positive relationship between hepatic iron stores and serum hepcidin level across all HFE genotypes. These data suggest that body iron stores are the major determinant of hepcidin regulation in NAFLD, regardless of HFE genotype. A potential role for H63D mutations in NAFLD pathogenesis is possible through iron-independent mechanisms.

SUBMITTER: Nelson JE

PROVIDER: S-EPMC3462887 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

Nelson James E JE Brunt Elizabeth M EM Kowdley Kris V KV

Hepatology (Baltimore, Md.) 20120920 5

<h4>Unlabelled</h4>Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic iron deposition, and histology in nonalcoholic fatty liver disease (NAFLD). Single-nucleotide polymorphism genotyping for C282Y (rs1800562) and H63D (rs1799945) HFE mutations was performed in 786 adult subjects in the NASH Clinical Resea ...[more]

PMID: 22611049

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Project description:BACKGROUND:Hepcidin is an iron regulating hormone, and exercise-induced hepcidin elevation is suggested to increase the risk of iron deficiency among athletes. OBJECTIVE:We compared serum hepcidin responses to resistance exercise and endurance (cycling) exercise. METHODS:Ten males [mean ± standard error: 172 ± 2 cm, body weight: 70 ± 2 kg] performed three trials: a resistance exercise trial (RE), an endurance exercise trial (END), and a rest trial (REST). The RE consisted of 60 min of resistance exercise (3-5 sets × 12 repetitions, 8 exercises) at 65% of one repetition maximum, while 60 min of cycling exercise at 65% of [Formula: see text] was performed in the END. Blood samples were collected before exercise and during a 6-h post-exercise (0h, 1h, 2h, 3h, 6h after exercise). RESULTS:Both RE and END significantly increased blood lactate levels, with significantly higher in the RE (P < 0.001). Serum iron levels were significantly elevated immediately after exercise (P < 0.001), with no significant difference between RE and END. Both the RE and END significantly increased serum growth hormone (GH), cortisol, and myoglobin levels (P < 0.01). However, exercise-induced elevations of GH and cortisol were significantly greater in the RE (trial × time: P < 0.001). Plasma interleukin-6 (IL-6) levels were significantly elevated after exercise (P = 0.003), with no significant difference between the trials. Plasma hepcidin levels were elevated after exercise (P < 0.001), with significantly greater in the RE (463 ± 125%) than in the END (137 ± 27%, P = 0.03). During the REST, serum hepcidin and plasma IL-6 levels did not change significantly. CONCLUSION:Resistance exercise caused a greater exercise-induced elevation in hepcidin than did endurance (cycling) exercise. The present findings indicate that caution will be required to avoid iron deficiency even among athletes in strength (power) types of events who are regularly involved in resistance exercise.

Dataset Information

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

Publications

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

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