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A proposed model for cortisol effect on growth and immune suppression in trout liver. Stressed levels of cortisol elevate SOCS transcript levels and reduce GH signaling and the corresponding IGF-1 expression in rainbow trout liver by preventing STAT5 phosphorylation and decreasing total JAK2 protein expression. The cortisol-induced upregulation of SOCS may be playing a role in the suppression of LPS-induced IL-6 expression (a cytokine signaling through the JAK/STAT pathway). Immune challenge with LPS may indirectly inhibit GH signaling by elevating plasma cortisol levels or directly inhibit GH signaling and the corresponding IGF-1 expression by downregulating growth hormone receptors 1 and 2 and by preventing STAT5 phosphorylation.
Source publication
Chronic stress is a major factor in the poor growth and immune performance of salmonids in aquaculture. However, the molecular mechanisms linking stress effects to growth and immune dysfunction is poorly understood. The suppressors of cytokine signaling (SOCS), a family of genes involved in the inhibition of JAK/STAT pathway, negatively regulates g...
Citations
... These maladaptive alterations are energetically costly, since energy substrates mobilised by cortisol are reallocated from other essential processes, such as growth, immune function or reproduction. Chronic stress and the associated cortisol elevation have therefore been suggested as key factors in reduced growth rates of fish (Philip and Vijayan 2015). In the present study, the cacna1c and cacna1g enriched in the cortisol synthesis and secretion pathway include those enriched in the aldosterone synthesis and secretion pathway. ...
Large yellow croaker (Larimichthys crocea) is an important aquaculture species in China. This study analysed whole-genome methylation differences in liver tissues of young fish under different hypoxic and acidification conditions. Differentially methylated regions (DMRs) and differentially methylated genes (DMGs) were identified. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analyses of DMGs were conducted to explore the mechanism of coping with hypoxic acidification. The main methylation type was CG, accounting for > 70% of total methylation, significantly higher than CHG and CHH methylation types. GO enrichment analysis of DMGs revealed strong enrichment of nervous system development, cell periphery, plasma membrane, cell junction organisation, cell junction, signalling receptor activity, molecular sensor activity, cell-linked tissue junction organisation, cell–cell adhesion and nervous system development. KEGG enrichment analysis of DMR-related genes identified cell adhesion molecules, cortisol synthesis and secretion and aldosterone synthesis and secretion as the three key pathways regulating the physiological responses to hypoxia and acidification. Long-term hypoxic and acidification stress affected the immune system, nervous system and stress responses of large yellow croaker. Whole-genome sequencing analysis of exposed tissues was used to investigate changes that occur in L. crocea in response to hypoxic and acidic conditions at the DNA methylation level. The findings contribute to our comprehensive understanding of functional methylation in large yellow croaker and will support future research on the response mechanisms of this species under different environmental pressures.
... In addition, we identified selective signatures of the suppressor of the cytokine signalling-2 (socs-2) gene, an important negative regulator of the GH/IGF-1 axis. The product of this gene can competitively bind to Igf-1r and thereby impede the function of IGF-1 in various species (Greenhalgh et al., 2002;Horvat & Medrano, 2001;Liu et al., 2006;Philip & Vijayan, 2015). ...
Consideration of the thermal adaptation of species is essential in both evolutionary biology and climate‐change biology because it frequently leads to latitudinal gradients of various phenotypes among populations. The spotted sea bass (Lateolabrax maculatus) has a broad latitudinal distribution range along the marginal seas of the Northwest Pacific and thus provides an excellent teleost model for population genetic and climate adaptation studies. We generated over 8.57 million SNP loci using whole‐genome resequencing from 100 samples collected at 14 geographic sites (five or ten samples per site). We estimated the genetic structure of the sampled fish and clustered them into three highly differentiated populations. The genetic differentiation pattern estimated by multivariable models combining geographic distance and sea surface temperature differences suggests that isolation by distance and isolation by environment both have significant effects on this species. Further investigation of genome‐wide evolutionary signatures of climate adaptation identified many genes related to growth, muscle contraction, and vision that are under positive natural selection. Moreover, the contrasting patterns of natural selection in high‐latitude and low‐latitude populations prompted different strategies of trade‐offs between growth rate and other traits that may play an essential role in adaptation to different local climates. Our results offer an opportunity to better understand the genetic basis of the phenotypic variation in eurythermal fishes inhabiting different climatic regions.
... Yet the exact role of cytokines within the stress axes is ill-defined (Tort and Balasch, 2022). What has been described is mainly the up and downregulation of pro and anti-inflammatory cytokines by glucocorticoids in various fish species (Verburg-van Kemenade et al., 2011;Nardocci et al., 2014;Philip and Vijayan, 2015;Yarahmadi et al., 2016;Khansari et al., 2017b;Reyes-López et al., 2018). The increase in cytokines following inflammation has the potential to activate the stress response, as is apparent with interleukin-6, where it has a role as a stimulating factor of CRH, prolactin, growth hormones, and ACTH, which in turn will increase cortisol (Calcagni and Elenkov, 2006;Žarković et al., 2008). ...
... Sveen et al. (2018) showed that chronically stressed Atlantic salmon with wounds did not significantly differ in body weight compared to control fish and that the control fish were slightly larger at the end of the experiment (57 days); these results are similar to our findings. This leads to the possible theorisation that wounded fish under stress cannot completely shift energy out of growth and reduce cytokine signalling, which happens when wounds are not present (Philip and Vijayan, 2015). This may be due to the need for growth factors and cytokines in the wound-healing process. ...
The desire to understand fish welfare better has led to the development of live monitoring sensor tags embedded within individuals for long periods. Improving and understanding welfare must not come at the cost of impaired welfare due to a tag's presence and implantation process. When welfare is compromised, the individual will experience negative emotions such as fear, pain, and distress, impacting the stress response. In this study, Atlantic salmon (Salmo salar) underwent surgical implantation of a dummy tag. Additionally, half of this group was introduced to daily crowding stress. Both groups and an untagged group were followed for 8 weeks using triplicate tanks per group. Sampling took place once a week, and where stress was given, it was conducted 24 h before sampling. Stress-related measurements were taken to understand if tagging caused chronic stress and explore the chronic stress response and its impact on wound healing. Primary stress response hormones measured included CRH, dopamine, adrenocorticotropic hormone, and cortisol. Secondary stress response parameters measured included glucose, lactate, magnesium, calcium, chloride, and osmolality. Tertiary stress response parameters measured included weight, length, and five fins for fin erosion. Wound healing was calculated by taking the incision length and width, the inflammation length and width, and the inside wound length and width. The wound healing process showed that stressed fish have a larger and longer-lasting inflammation period and a slower wound healing process, as seen from the inside wound. The tagging of Atlantic salmon did not cause chronic stress. In contrast, daily stress led to an allostatic overload type two response. ACTH was elevated in the plasma after 4 weeks, and cortisol followed elevation after 6 weeks, highlighting a breakdown of the stress regulation. Fin erosion was elevated alongside cortisol increase in the stressed group. This data suggests that tagging previously unstressed fish in a controlled environment does not negatively affect welfare regarding stress responses. It also indicates that stress delays wound healing and increases the inflammatory response, highlighting how continued stress causes a breakdown in some stress responses. Ultimately, the tagging of Atlantic salmon can be successful under certain conditions where proper healing is observed, tag retention is high, and chronic stress is not present, which could allow for the possible measurement of welfare indicators via smart-tags.
... Interestingly, NF-kB signalling pathway was still the main response pathway in the genome-wide association study (GWAS) of Aeromonas septicemia disease even though there were differences in experimental treatments compare to this study (24). It is worth noting that our results appear to counter the discussion regarding the inhibitory regulation of cytokines from cortisol (68)(69)(70). Here, we considered a possible reason for this observation, where the duration regulation of cortisol on the time axis does not appear to be unidirectional (4,54). ...
In China, channel catfish (Ictalurus punctatus) is an important aquaculture species; however, haemorrhagic disease (Aeromonas hydrophila induced disease) in these fish has caused tremendous economic loss due to high morbidity and mass mortality in the breeding industry. The role of cortisol in bacterial diseases, particularly in the acute phase, remains unclear. In this study, liver transcriptome (RNA-seq) and chromatin accessibility (ATAC-seq) analyses were employed to investigate the early functional role of cortisol in Aeromonas hydrophila-stimulated responses. Our experiments confirmed that A. hydrophila infection can initially significantly increase serum cortisol levels at 1 h after infection. At this time point, the increased serum cortisol levels can significantly regulate A. hydrophila-regulated genes by affecting both transcriptome and chromatin accessibility. Cross-analysis of RNA-seq and ATAC-seq revealed that a certain gene group (92 target_DEGs) was regulated at an early time point by cortisol. KEGG enrichment analysis revealed that the top three pathways according to target_DEGs were cancer, glutathione metabolism, and the Notch signalling pathway. The protein-protein interaction analysis of target_DEGs revealed that they may be primarily involved in cell proliferation, CD8⁺ T cell function, glutathione synthesis, and activation of the NF-κB signalling pathway. This suggests that after the emergence of immune stress, the early regulation of cortisol is positive against the immune response. It is possible that in this situation, the animal is attempting to avoid dangerous situations and risks and then cope with the imbalance produced by the stressor to ultimately restore homeostasis. Our results will contribute to future research on fish and provide valuable insight regarding the mechanism of immune regulation by cortisol and the study of bacterial haemorrhagic disease in channel catfish.
... As glucocorticoids, a primary function of corticosteroids in fish is to stimulate gluconeogenesis in the liver via upregulation of the major enzymes in this pathway, and glucocorticoid signaling is further implicated in the regulation of glycogen, lipid, and protein stores (Mommsen et al., 1999). Moreover, sustained elevations in circulating corticosteroid levels facilitates the redirection of energy utilization toward essential life-sustaining functions by inhibiting the digestive (Barton et al., 1987;Pfalzgraff et al., 2021), immune (Fabbri and Moon, 2016;Philip and Vijayan, 2015;Pickering and, Pottinger, 1989), and reproductive systems (Pankhurst, 2016;Pankhurst and Van Der Kraak, 1997). As mineralocorticoids, corticosteroids contribute to the maintenance of ion and water homeostasis by regulating ion transporter expression in ionocytes such as the chloride cells of the gills . ...
Endocrine systems are regulators of physiological responses to environmental conditions, acting as key transmitters of external and internal cues, and can therefore provide valuable insights to help address pressing issues in fish conservation biology. In this review, after a brief overview of the endocrine systems involved in regulating stress, growth, and reproduction, we examine how fish endocrinologists are developing and applying new tools to monitor, conserve, and assist threatened and endangered wild fish populations. Specifically, we provide examples of how endocrine signals are used to guide the development of conservation hatcheries, to reveal how exposure to environmental stressors can affect development and growth, to enable assisted reproduction, to mitigate the impacts of climate change and endocrine-disrupting chemicals on fish reproduction, and to facilitate the management of invasive species. We also examine how non-invasive sampling techniques, profiling of steroid hormones, and the integration of endocrinology with emerging fields such as ecotoxicogenomics and host-microbiome interactions will have impacts on future conservation efforts. Finally, we identify limitations for the broader application of endocrinology in fish conservation and opportunities for fish endocrinologists to make meaningful contributions to the most urgent conservation challenges of our time.
... Important negative cytokine regulatory factors include suppressor of cytokine signaling 1 (SOCS1), suppressor of cytokine signaling 2 (SOCS2), and interleukin-1 receptorassociated kinase M (IRAK-M) (39). GCs can improve the inhibitory impact of SOCS1 and SOCS2 on the JAK/STAT inflammatory signaling pathway, as well as the inhibitory effect of IRAK-M on the Toll-like receptor 4 (TLR4) inflammatory signaling pathway (40,41). Nucleotide-binding oligomerisation domain-like receptors (NLRs) Family Pyrin Domain Containing 3 (NLRP3) is related to innate immunity and can produce proinflammatory cytokines via caspase-1 (42). ...
Liver failure is characterized by serious liver decompensation and high mortality. The activation of systemic immune responses and systemic inflammation are widely accepted as the core pathogenesis of liver failure. Glucocorticoids (GCs) are most regularly utilized to suppress excessive inflammatory reactions and immunological responses. GCs have been used in the clinical treatment of liver failure for nearly 60 years. While there has been no unanimity on the feasibility and application of GC treatment in liver failure until recently. The most recent trials have produced conflicting results when it comes to the dose and time for GC therapy of different etiology of liver failure. Our review outlines the issues and options in managing GC treatment in liver failure based on an investigation of the molecular mechanism that GC may give in the treatment.
... Further, the delousing stress significantly downregulated the mRNA expression of all analysed immune genes (IFN-γ, TNF-α, TGFβ and IL4/13a) at 1 h post-stress, which is concurrent with increased cortisol production. The similar down-regulation of immune response upon stress exposure has been reported previously in mammals (75,76) and in fish (77,78) . ...
Atlantic salmon were fed diets containing graded levels of EPA+DHA (1.0, 1.3, 1.6, and 3.5 % in the diet) and one diet with 1.3 % of EPA+DHA with reduced total fat content. Fish were reared in sea cages from ∼275 g until harvest size (∼5 kg) and were subjected to delousing procedure (∼ 2.5 kg), with sampling pre-, 1h and 24 h post-stress. Delousing stress affected plasma cortisol and hepatic mRNA expression of genes involved in oxidative stress and immune response, but with no dietary effects. Increasing EPA+DHA levels in the diet increased the trace mineral levels in plasma and liver during mechanical delousing stress period and whole body at harvest size. The liver Se, Zn, Fe, Cu, and Mn and plasma Se levels were increased in fish fed a diet high in EPA+DHA (3.5 %) upon delousing stress. Furthermore, increased dietary EPA+DHA caused a significant increase in mRNA expression of HAMP, which is concurrent with downregulated TFR expression levels. High dietary EPA+DHA also significantly increased the whole-body Zn, Se, and Mn levels at harvest size fish. Additionally, the plasma and whole-body Zn status increased respectively during stress and at harvest size in fish fed reduced-fat diet with less EPA+DHA. As the dietary upper limits of Zn and Se are legally added to the feeds, and play important roles in maintaining fish health, knowledge on how the dietary fatty acid composition and lipid level affect body stores of these minerals is crucial for the aquaculture industry.
... These maladaptive alterations are energetically costly since energy substrates mobilized by cortisol are reallocated from other essential processes, such as growth, immune function, or reproduction (Schreck and Tort, 2016). Chronic stress, and the associated cortisol elevation, have therefore been suggested as key factors in reduced growth rates of fish (Philip and Vijayan, 2015). Most studies have assessed the short-term metabolic actions of this hormone. ...
Chronic elevation of circulating cortisol is known to have deleterious effects on fish, but information about the consequences of prolonged cortisol elevation on the metabolism of fish is scarce. To test the effects of chronic cortisol elevation on the aerobic performance of rainbow trout, we examined how two severities of chronically elevated plasma cortisol levels affected the oxygen uptake during rest and after exhaustive exercise using a high (HC) and a medium cortisol (MC) treatment. High cortisol doses significantly affected standard (SMR) and maximum metabolic rates (MMR) compared to control fish. In comparison, the medium cortisol treatment elevated MMR but did not significantly influence SMR compared to a sham group (S) and control group (C). The medium cortisol treatment resulted in a significantly increased metabolic scope due to an elevation of MMR, an effect that was abolished in the HC group due to co-occuring elevations in SMR. The elevated SMR of the HC-treated fish could be explained by increased in vitro oxygen uptake rates (MO 2) of specific tissues, indicating that the raised basal metabolism was caused, in part, by an increase in oxygen demand of specific tissues. Haematological results indicated an increased reliance on anaerobic metabolic pathways in cortisol-treated fish under resting conditions.
... In pre-spawning, JAK/STAT signaling pathway is down regulated but in spawning phase, it is up regulated for growth and increase in innate immunity of Rainbow trout fish [130] PCK1 PCK1 is reported to have seasonal expression in liver of animals. In fish,this gene is associated with regulation of gluconeogenesis, oxidative phosphorylation and growth. ...
Background
Carp fish, rohu ( Labeo rohita Ham.) is important freshwater aquaculture species of South-East Asia having seasonal reproductive rhythm. There is no holistic study at transcriptome level revealing key candidate genes involved in such circannual rhythm regulated by biological clock genes (BCGs). Seasonality manifestation has two contrasting phases of reproduction, i.e., post-spawning resting and initiation of gonadal activity appropriate for revealing the associated candidate genes. It can be deciphered by RNA sequencing of tissues involved in BPGL (Brain-Pituitary-Gonad-Liver) axis controlling seasonality. How far such BCGs of this fish are evolutionarily conserved across different phyla is unknown. Such study can be of further use to enhance fish productivity as seasonality restricts seed production beyond monsoon season.
Result
A total of ~ 150 Gb of transcriptomic data of four tissues viz., BPGL were generated using Illumina TruSeq. De-novo assembled BPGL tissues revealed 75,554 differentially expressed transcripts, 115,534 SSRs, 65,584 SNPs, 514 pathways, 5379 transcription factors, 187 mature miRNA which regulates candidate genes represented by 1576 differentially expressed transcripts are available in the form of web-genomic resources. Findings were validated by qPCR. This is the first report in carp fish having 32 BCGs, found widely conserved in fish, amphibian, reptile, birds, prototheria, marsupials and placental mammals. This is due to universal mechanism of rhythmicity in response to environment and earth rotation having adaptive and reproductive significance.
Conclusion
This study elucidates evolutionary conserved mechanism of photo-periodism sensing, neuroendocrine secretion, metabolism and yolk synthesis in liver, gonadal maturation, muscular growth with sensory and auditory perception in this fish. Study reveals fish as a good model for research on biological clock besides its relevance in reproductive efficiency enhancement.
... The highest number of CD4-2 + T cells was observed in the liver at 7 dpi, which suggests direct involvement of virus-specific Th1 (CD4-2 + ) T cells during the peak of acute infection [40]. Although the liver-related immune response in teleost has not been investigated much yet, the hepatic immune of fish has recently been reporting including rainbow trout (Oncorhynchus mykiss), Arctic charr (Salvelinus alpinus), and olive flounder (Paralichthys olivaceus) [41][42][43][44][45][46]. Early infection with VHSV has been shown to increase transcription levels of some genes in the liver of rainbow trout, namely CD3 and CD4 [45], while CD4 and CD8 were seen to be increased in olive flounder [43]. ...
... Although the liver-related immune response in teleost has not been investigated much yet, the hepatic immune of fish has recently been reporting including rainbow trout (Oncorhynchus mykiss), Arctic charr (Salvelinus alpinus), and olive flounder (Paralichthys olivaceus) [41][42][43][44][45][46]. Early infection with VHSV has been shown to increase transcription levels of some genes in the liver of rainbow trout, namely CD3 and CD4 [45], while CD4 and CD8 were seen to be increased in olive flounder [43]. Furthermore, intrahepatic immune cells (IHICs) act as resident antigen-presenting cells that prime naïve T cells in the early stage of viral infection in teleosts [47]. ...
Viral hemorrhagic septicemia (VHS), caused by viral hemorrhagic septicemia virus (VHSV), is a viral disease affecting teleosts, and is the major cause of virus-related deaths in olive flounder (Paralichthys olivaceus). Research has focused on ways to control VHS, and recently, the use of polyinosinic-polycytidylic acid poly (I:C)-potentiated vaccination has been investigated, whereby fish are injected with poly (I:C) and then with live pathogenic virus, resulting in a significant decrease in VHSV-related mortality. T cell responses were investigated in the present study after vaccinating olive flounder with poly (I:C)-potentiated vaccination to understand the ability of poly (I:C) to induce T cell immunity. Stimulation of T cell responses with the poly (I:C)-potentiated vaccination was confirmed by examining levels of CD3+ T cells, CD4-1+ T cells and CD4-2+ T cells. Higher levels of CD4-2+ T cells were found in vaccinated fish than CD4-1+ T cells, believed to result from a synergistic effect between poly (I:C) administration and pathogenic VHSV immunization. More importantly, the role of CD4-2+ T cells in the antiviral response was clearly evident. The results of this study suggest that the outstanding protection obtained with the poly (I:C)-potentiated vaccination is due to the robust immune response initiated by the CD4-2+ T cells.
