Starvation alters the liver transcriptome of the innate immune response in Atlantic salmon (Salmo salar)

Abstract

BackgroundThe immune response is an energy demanding process, which has effects in many physiological pathways in the body including protein and lipid metabolism. During an inflammatory response the liver is required to produce high levels of acute phase response proteins that attempt to neutralise an invading pathogen. Although this has been extensively studied in both mammals and fish, little is known about how high and low energy reserves modulate the response to an infection in fish which are ectothermic vertebrates. Food withdrawal in fish causes a decrease in metabolic rate so as to preserve protein and lipid energy reserves, which occurs naturally during the life cycle of many salmonids. Here we investigated how the feeding or fasting of Atlantic salmon affected the transcriptional response in the liver to an acute bacterial infection.ResultsTotal liver RNA was extracted from four different groups of salmon. Two groups were fed or starved for 28 days. One of each of the fed or starved groups was then exposed to an acute bacterial infection. Twenty four hours later (day 29) the livers were isolated from all fish for RNA extraction. The transcriptional changes were examined by micro array analysis using a 17 K Atlantic salmon cDNA microarray. The expression profiling results showed major changes in gene transcription in each of the groups. Enrichment for particular biological pathways was examined by analysis of gene ontology. Those fish that were starved decreased immune gene transcription and reduced production of plasma protein genes, and upon infection there was a further decrease in genes encoding plasma proteins but a large increase in acute phase response proteins. The latter was greater in magnitude than in the fish that had been fed prior to infection. The expression of several genes that were found altered during microarray analysis was confirmed by real time PCR.ConclusionsWe demonstrate that both starvation and infection have profound effects on transcription in the liver of salmon. There was a significant effect on the transcriptional response to infection depending on the prior feeding regime of the fish. It is likely that the energy demands on protein synthesis for acute phase response proteins are relatively high in the starved fish which have reduced energy reserves. This has implications for dietary control of fish if an immune response is anticipated.

Tissue-specific molecular immune response to lipopolysaccharide challenge in emaciated anadromous Arctic charr

“…A key finding from this study was that LPS-mediated upregulation of cytokines, including IL-1b and IL-8 were observed in both the fed and fasted Arctic charr. This is unlike other animal models where even short term starvation reduces the capacity for immune response activation (Martin et al, 2010). IL-1b is important in initiating inflammatory responses while IL-8 is a potent neutrophil chemotactic factor (Fast et al, 2007) and, together, they act as key mediators of innate immunity.…”

“…The temporal increase in liver IL-8 levels in the control fed group at 96 h postinjection may be due to the stress of handling and injection (Fast et al, 2007). During an inflammatory response the liver synthesizes high levels of APPs that assists with the neutralization of invading pathogens (Martin et al, 2010). SAA is a positive APP, whose levels have been shown to increase during inflammation (Uhlar and Whitehead, 1999).…”

“…However, very little is known about the effect of dietary restriction on the immune response in fish. A recent study showed that in the Atlantic salmon (Salmo salar), starvation for 28 days led to a reduction in mRNA abundance of immune-related genes in the liver (Martin et al, 2010). Also, starvation for 31 days decreased the non-specific immune parameters, including haemagglutinating activity and respiratory burst activity in the sea bass (Dicentrarchus labrax) and blackspot sea bream (Pagellus bogaraveo) (Caruso et al, 2011).…”

“…Fasting leads to a negative energy balance and can restrict energy demanding pathways, including mounting an immune response (Berczi, 1986;Houston et al, 2007;Martin et al, 2010). Most studies that have examined the direct effects of nutritional status on the immune response have focused on mammalian models and showed a decreased capacity to defend against infection (Sun et al, 2001;Walrand et al, 2001).…”

“…While reduced capacity for immune response activation in response to negative energy balance appears to be the norm in most animals (Martin et al, 2010;Berczi, 1986), those studies utilized animal models that do not naturally experience extended fasting. We asked the question whether animals exhibiting extreme adpatations, including extended fasting as part of a life-history strategy, show the same degree of immune response to immunostimulants as fed animals.…”