Effects of sustained exercise on GH-IGFs axis in gilthead sea bream (Sparus aurata)

Abstract

The endocrine system regulates growth mainly through the growth hormone (GH)/insulin-like growth factors (IGFs) axis and, although exercise promotes growth, little is known about its modulation of these factors. The aim of this work was to characterize the effects of 5 wk of moderate sustained swimming on the GH-IGFs axis in gilthead sea bream fingerlings. Plasma IGF-I/GH ratio and tissue gene expression of total IGF-I and three splice variants, IGF-II, three IGF binding proteins, two GH receptors, two IGF-I receptors, and the downstream molecules were analyzed. Fish under exercise (EX) grew more than control fish (CT), had a higher plasma IGF-I/GH ratio, and showed increased hepatic IGF-I expression (mainly IGF-Ia). Total IGF-I expression levels were similar in the anterior and caudal muscles; however, IGF-Ic expression increased with exercise, suggesting that this splice variant may be the most sensitive to mechanical action. Moreover, IGFBP-5b and IGF-II increased in the anterior and caudal muscles, respectively, supporting enhanced muscle growth. Furthermore, in EX fish, hepatic IGF-IRb was reduced together with both GHRs; GHR-II was also reduced in anterior muscle, while GHR-I showed higher expression in the two muscle regions, indicating tissue-dependent differences and responses to exercise. Exercise also increased gene and protein expression of target of rapamycin (TOR), suggesting enhanced muscle protein synthesis. Altogether, these data demonstrate that moderate sustained activity may be used to increase the plasma IGF-I/GH ratio and to potentiate growth in farmed gilthead sea bream, modulating the gene expression of different members of the GH-IGFs axis (i.e., IGF-Ic, IGF-II, IGFBP-5b, GHR-I, and TOR).

Regulatory mechanisms involved in muscle and bone remodeling during refeeding in gilthead sea bream

“…Muscle igfbps also responded differently to the treatment and while expression of igfbp1 or igfbp4 was unchanged, igfbp5 significantly decreased in fasting and recovered progressively after 7 days of refeeding. This is in agreement with the anabolic function attributed to igfbp5, which has been identified as a good growth marker in gilthead sea bream 40 . Similar responses were detected in some species 41,42 ; but not in others 35,43,44 , although such a decrease is analogous to the Igfbp3 plasma levels determined in fasted coho and chinook salmon [45][46][47] , suggesting a similar response of these two igfbps to long term food deprivation in different fish species.…”

“…These patterns coincide with the differential function attributed to each receptor in gilthead sea bream and other fish species, being Ghr1 anabolic and Ghr2 catabolic 23,48 . Thus, in gilthead sea bream the growth enhancement caused by sustained exercise was followed by an increase in ghr1 expression and a decrease in ghr2 expression in muscle 40 . Similarly in this species, Gh treatment induced in muscle an increase of ghr1 expression but not ghr2 23 .…”

Co-expression Analysis of Sirtuins and Related Metabolic Biomarkers in Juveniles of Gilthead Sea Bream (Sparus aurata) With Differences in Growth Performance

“…The same relationship held true for markers of the GH/IGF axis, and we found that plasma level of IGF-I closely reflected differences in growth potentiality between fish strains, as previously observed when comparing the growth performance of gilthead sea bream with that of the stress sensitive common dentex (Bermejo-Nogales et al, 2007 ). Experimental evidence regarding the gilthead sea bream also indicates that IGF-I is highly responsive to changes in growth performance due to biotic and abiotic factors, including season and developmental stage (Mingarro et al, 2002 ; Saera-Vila et al, 2007 ), ration size (Pérez-Sánchez et al, 1995 ), crowding and handling stress (Rotllant et al, 2001 ), physical activity (Vélez et al, 2016 ), hypoxia (Martos-Sitcha et al, 2017 ) and dietary protein and lipid source (Gómez-Requeni et al, 2004 ; Benedito-Palos et al, 2007 ; Ballester-Lozano et al, 2015 ; Simó-Mirabet et al, 2017b ). Most of these changes in circulating levels of IGF-I are inversely correlated with plasma levels of GH due to the IGF-I feedback inhibition of pituitary GH synthesis and secretion (Pérez-Sánchez, 2000 ).…”

Ghrelin and Its Receptors in Gilthead Sea Bream: Nutritional Regulation

“…Additionally, 3 fish were sacrificed and sampled for 17 distinct tissues and/or organs. RNA was obtained from tissue samples (30–100 mg) or from the whole pituitary gland and brain with 1 mL of TRI Reagent Solution (Applied Biosystems, Alcobendas, Spain) and reverse transcribed following the procedures previously described ( 26 ). Briefly, 1 μg of RNA was treated with DNase I (Life Technologies, Alcobendas, Spain) following the manufacturer's instructions to remove genomic DNA.…”

“…The mRNA transcript levels were examined by quantitative real-time PCR (qPCR) according to the requirements of MIQUE guidelines ( 33 ) in a CFX384™ Real-Time System (Bio-Rad, El Prat de Llobregat, Spain). All reactions were performed in the conditions previously described ( 26 ). The primers used are listed in Table 1 .…”