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Fabian Grammes defended his thesis on May 27th 2011
Ane Gro Siri SkjelfjordCardiac and immune modulatory effects of tetradecylthioactetic acid (TTA) in Atlantic salmon (Salmo salar L.)
Summary from the thesis - PhD thesis 2011:20
Tetradecylthioacetic acid (TTA) is a bioactive fatty acid with pleiotropic effects that are presumed to be mediated, almost entirely, via activation of peroxisome proliferator activated receptors (PPARs). Due to their effects on important pathways, such as fatty acid oxidation (FAO) and inflammation in numerous tissues, TTA and other PPAR activators have been the subject of extensive research in mammalian model organisms and also in humans. However the effects have been sparsely studied in Atlantic salmon (Salmo salar, L.). The aim of the thesis was to evaluate biological effects of tetradecylthioacetic acid (TTA) as a functional feed ingredient for Atlantic salmon.
Paper-I describes how (0+) Atlantic salmon fed a TTA supplemented diet showed a significant lower mortality during a natural outbreak of heart and skeletal muscle inflammation (HSMI) at the production site. HSMI is a relatively "new" disease in Atlantic salmon aquaculture that accounts for significant production losses. The effect of increased survival correlated with the increased cardiac gene expression of PPARα and PPARβ/δ, and also an increase in relative heart weight in the fish fed TTA. The effects of TTA on gene expression and survival were found 6 weeks after TTA feeding stopped.
We speculated that the increased expression of PPARs may actually be related to the increase in survival. However, confounding effects of the HSMI infection could not be excluded. The recent discovery and sequencing of the virus believed to be the infectious agent causing HSMI [1] enabled us to test the relationship between cardiac viral titers and expression of PPARs.
Paper-II shows that the cardiac gene expression levels of PPARα and PPARβ/δ were not effected by the viral titer and thus added confidence to our hypothesis that the effects were the result of the dietary TTA supplementation. The gene expression results from that study further indicated that TTA increased the expression of the immune genes tumor necrosis factor α (TNFα), vascular cell adhesion molecule 1 (VCAM1), immunoglobulin M (1gM) and cluster of differentiation 8α (CD8α). Thus indicating an increased adaptive immune response in TTA fed Atlantic salmon.
Paper-III describes the transcriptional effects of TTA in heart samples of Atlantic salmon unaffected by viral diseases, on a "genome-wide" scale. The results confirm profound effects of TTA on the cardiac transcription. Similarly to the results obtained in Paper-I, the transcriptional results were observed after the TTA feeding stopped. However, based on the results from Microarray and qRT-PCR, the results suggest a pattern whereby the hearts of TTA fed fish show increased cardiac performance, as indicated by an increased capacity for FAO, glycolysis, TCA-cycle activity as well as cardiac contractility and growth. The increased cardiac performance that we found for TTA fed fish in this study may offer significant benefits for fish in stressful aquaculture situations. Despite the impressive number of differentially expressed genes in this study, nearly none of the genes were implicated in immune modulation.
Paper-I, Paper-II suggested that TTA as dietary supplement offers significant benefits for Atlantic salmon challenged by viral diseases. The results from Paper-II further indicated that TTA has immune modulatory functions, which have been well documented for PPAR agonists and also TTA in mammals, but not yet in Atlantic salmon.
In Paper-IV the immune modulatory functions of TTA were investigated, in vitro, in the macrophage-like cell line Atlantic salmon kidney (ASK). The cells were treated with TTA and the dsRNA analogue poly(I:C), to simulate viral infection in a factorial designed experiment and the transcriptional effects were analyzed by microarray. The results showed that TTA had significant immune modulatory effects, attenuating the transcriptional response of a subset of genes to poly(I:C). Additionally TTA increased the capacity for FAO and increased transcription of anti-inflammatory genes. The expression profile suggested that TTA directed the macrophage-like cell line more towards an alternatively activated (anti-inflammatory) (M2) state.
Our findings demonstrate that TTA triggers profound effects in the Atlantic salmon ventricle which have never before been investigated. The results further suggest that TTA directly increases the capacity of cardiac performance. Additionally, TTA can reduce the pro-inflammatory response in the macrophage-like cell line ASK. In light of increasing challenges on the cardiac performance through diseases, nutrition and the aquaculture environment, these TTA effects may offer significant benefits for the overall fish health.
Oppdatert: 20.06.11
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