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The Ghrelin Analog GHRP-6, Delivered Through Aquafeeds, Modulates the Endocrine and Immune Responses of Sparus aurata Following IFA Treatment
by
, , , , , and
Leandro Rodríguez-Viera
1,*,
Anyell Caderno
1,
Rebeca Martinez
2,
Gonzalo Martinez-Rodríguez
3
,
Milagrosa Oliva
1,
Erick Perera
3,
Juan Miguel Mancera
1
and
Juan Antonio Martos-Sitcha
1,* 1
Department of Biology, Faculty of Marine and Environmental Sciences, Instituto Universitario de Investigación Marina (INMAR), University of Cadiz, Campus de Excelencia Internacional del Mar (CEIMAR), Puerto Real, 11519 Cadiz, Spain
2
Aquatic Biotechnology Project, Center for Genetic Engineering and Biotechnology, Havana 10900, Cuba
3
Andalusian Institute of Marine Sciences (ICMAN), Spanish National Research Council (CSIC), Puerto Real, 11519 Cadiz, Spain
*
Authors to whom correspondence should be addressed.
Biology 2025, 14(8), 941; https://doi.org/10.3390/biology14080941
Submission received: 28 June 2025
/
Revised: 18 July 2025
/
Accepted: 23 July 2025
/
Published: 25 July 2025
(This article belongs to the Special Issue Aquatic Animal Nutrition and Feed)
Simple Summary
Aquaculture is growing rapidly, and improving the health and resilience of farmed fish is essential for sustainable production. This study tested whether a small synthetic molecule, GHRP-6, could be used as a feed additive to support the immune system of gilthead sea bream, an important farmed fish in the Mediterranean. After several weeks of feeding fish with a diet enriched with GHRP-6, the animals were exposed to a mild immune challenge. The fish that received the GHRP-6 diet showed signs of better immune readiness, with increased levels of immune-related molecules in the blood and specific genes activated in key tissues. These fish also had lower stress hormone levels compared to the control group, suggesting a protective effect. Importantly, no damage was observed in their internal organs. Together, the results suggest that GHRP-6 may help fish respond better to immune challenges while keeping stress under control. This could make fish farming more efficient and reduce the need for other treatments. Further research is needed to understand how this compound works and whether it can help fish resist infections in the long term. This study shows that smart nutrition can be a powerful tool in modern aquaculture.
Abstract
The aquaculture industry has experienced considerable growth in recent decades, stimulating research into sustainable and functional feed formulations, mainly related to using high-quality, safe, and environmentally friendly feed ingredients. The employment of immunomodulatory additives is a promising strategy to enhance fish health and performance. In this study, the effects of the ghrelin analog GHRP-6 peptide included in the diet (500 µg/kg of feed) on the endocrine and immune responses of Sparus aurata following Incomplete Freund’s adjuvant (IFA) treatment were assessed. After 97 days, fish were intraperitoneally injected with 100 µL of saline solution or IFA/100 g fish and sampled 72 h post-injection. Our results indicated that fish fed GHRP-6 maintained stable plasma levels of lactate, triglycerides, and cortisol after IFA treatment, in contrast to control-fed fish, which showed significant metabolic stress. Circulating immunoglobulin levels enhanced significantly in the GHRP-6/IFA group, suggesting a stimulated humoral immune response. Transcriptomics analysis revealed that the anterior intestine was the most responsive tissue, with upregulation of il10, il15, il34, and mx1, indicating mucosal immune activation. In the spleen, GHRP-6-fed fish increased il8, il10, and ighm expression, highlighting a balanced pro- and anti-inflammatory response and support for adaptive immunity. Multivariate analysis confirmed that dietary GHRP-6 modulates immune gene expression in a tissue- and stimulus-specific manner, without inducing histological alterations in the intestine or spleen. Taken together, these preliminary results indicate that this peptide is a viable and safe dietary supplement to improve immune resilience and increase the production efficiency of S. aurata and suggest a protective effect on the fish’s immune system in this species.
