Project description:Background: Commercial Atlantic salmon is fed diets with high fat levels to promote fast and cost-eﬀective growth. To avoid negative impact of obesity, food additives that stimulate fat metabolism and immune function are of high interest. TTA, tetradecylthioacetic acid, is a synthetic fatty acid that stimulates mitochondrial β -oxidation most likely by activation of peroxysome proliferator-activated receptors (PPARs). PPARs are important transcription factors regulating multiple functions including fat metabolism and immune responses. Atlantic salmon experiments have shown that TTA supplemented diets signiﬁcantly reduce mortality during natural outbreaks of viral diseases, suggesting a modulatory role of the immune system. Results: To gain new insights into TTA eﬀects on the Atlantic salmon immune system, a factorial, high-throughput microarray experiment was conducted using a 44K oligo nucleotide salmon microarray SIQ2.0 and the Atlantic salmon macrophage-like cell line ASK. The experiment was used to determine the transcriptional eﬀects of TTA, the eﬀects of TTA in poly(I:C) elicited cells and the eﬀects of pretreating the cells with TTA. The expression patterns revealed that a large proportion of genes regulated by TTA were related to lipid metabolism and increased mitochondrial β -oxidation. In addition we found that for a subset of genes TTA antagonized the transcriptional eﬀects of poly(I:C). This, together with the results from qRT-PCR showing an increased transcription of anti-inﬂammatory IL10 by TTA, indicates anti-inﬂammatory eﬀects. Conclusions: We demonstrate that TTA has signiﬁcant eﬀects on macrophage-like salmon cells that are challenged by the artiﬁcial dsRNA poly(I:C). The immune stimulatory eﬀect of TTA in macrophages involves increased lipid metabolism and suppressed inﬂammatory status. Thus, suggesting that TTA directs the macrophage-like cells towards alternative, anti-inﬂammatory, activation. This has positive implications for TTA as a feed additive.

Project description:Background: Commercial Atlantic salmon is fed diets with high fat levels to promote fast and cost-eﬀective growth. To avoid negative impact of obesity, food additives that stimulate fat metabolism and immune function are of high interest. TTA, tetradecylthioacetic acid, is a synthetic fatty acid that stimulates mitochondrial β -oxidation most likely by activation of peroxysome proliferator-activated receptors (PPARs). PPARs are important transcription factors regulating multiple functions including fat metabolism and immune responses. Atlantic salmon experiments have shown that TTA supplemented diets signiﬁcantly reduce mortality during natural outbreaks of viral diseases, suggesting a modulatory role of the immune system. Results: To gain new insights into TTA eﬀects on the Atlantic salmon immune system, a factorial, high-throughput microarray experiment was conducted using a 44K oligo nucleotide salmon microarray SIQ2.0 and the Atlantic salmon macrophage-like cell line ASK. The experiment was used to determine the transcriptional eﬀects of TTA, the eﬀects of TTA in poly(I:C) elicited cells and the eﬀects of pretreating the cells with TTA. The expression patterns revealed that a large proportion of genes regulated by TTA were related to lipid metabolism and increased mitochondrial β -oxidation. In addition we found that for a subset of genes TTA antagonized the transcriptional eﬀects of poly(I:C). This, together with the results from qRT-PCR showing an increased transcription of anti-inﬂammatory IL10 by TTA, indicates anti-inﬂammatory eﬀects. Conclusions: We demonstrate that TTA has signiﬁcant eﬀects on macrophage-like salmon cells that are challenged by the artiﬁcial dsRNA poly(I:C). The immune stimulatory eﬀect of TTA in macrophages involves increased lipid metabolism and suppressed inﬂammatory status. Thus, suggesting that TTA directs the macrophage-like cells towards alternative, anti-inﬂammatory, activation. This has positive implications for TTA as a feed additive. Factorial designed experiment: factor pretreatment = 2 levels (Control, TTA); factor treatment = 4 levels (Control, TTA, polyIC, TTA+polyIC). Experiment was performed with 2 biological replicates (different passages). 1 array hybridization failed and was excluded from the dataset. Therefore total number of arrays =15

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