Publication: Report of "Host Defense Peptide Hepcidin 1 and Iron Overload Differentially Modulate Energy, Lipid, and Hepatic–Biliary Metabolic Pathways in Gilthead Seabream (Sparus aurata) Blood"
Date
2025
Authors
Laura García-Navarro ; Serna Duque, John Alberto ; Marín Parra, Claudia ; Esteban Abad, María de los Ángeles
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Facultades de la UMU::Facultad de Biología
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Esteban Abad, María de los Ángeles
Publisher
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Esteban Abad, María de los Ángeles
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DOI
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info:eu-repo/semantics/dataset
Description
Abstract
Hepcidin 1 (HDP, antimicrobial and iron regulator peptide) and iron overload are relevant in aquaculture, but their in vivo physiological effects in healthy fish are poorly characterized. This study evaluated how intraperitoneal injections of hepcidin 1, iron (iron-dextran), and a sequential treatment (iron and hepcidin 1) modulate the blood metabolome of gilthead sea bream (Sparus aurata) at 10 days, due to their adaptive role in response to systemic changes. Multivariate analyses showed metabolomic alterations in all three situations, although weak at 10 days; in the iron→hepcidin 1 group, the separation in PCA was not significant (P=0.247), suggesting overlap or absence of unidirectional shift. In all three treatments, 15 chemical superclasses were conserved (predominance of lipids), indicating quantitative reorganization. There was an activation of energy metabolism coupled with immune response, involving lipids, fatty acids, acyl-CoA/acylcarnitines, and signals from one-carbon metabolism (folate/serine/methionine) connected to NAD(H)/NADP(H) and redox balance, although several associations lost robustness (non-significant FDR), consistent with a return to homeostasis. Hepcidin 1 was associated with increased adenosine, Lys-Glu-Leu tripeptide, dodecanoylcarnitine and phosphoethanolamines/phosphocholines (LysoPE/PE/LysoPC), along with a decrease in exogenous compounds (e.g., erythromycin C, harzianopyridone), suggesting modulation of the gut–microbiota–barrier axis or hepatic-biliary clearance. Iron overload induced reprogramming compatible with reactive oxygen species management (increase in catalposide and L-NIL/L-NILL-type metabolites), lipid remodeling (decrease in PC/PE/PS, cholesterol esters and triglycerides), and greater mitochondrial mobilization of fatty acids (increase in linoleylcarnitine), without clear markers of peroxidation, liver damage or inflammation; herbicides (bensulfuron/sulfometuron methyl) were also reduced. In the iron and hepcidin 1 group, metabolites pointed to three axes: β-oxidation/fatty acid transport, phospho-/sphingolipid remodeling, and hepatic-biliary involvement with possible microbiota alteration. In conclusion, hepcidin 1 and iron modulate energy and lipid metabolism in gilthead sea bream blood, providing biomarkers and a framework for interpreting immunometabolic adaptations in aquaculture, although targeted validation of annotations and higher temporal resolution are required.
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