title: Nutrigenomic effects of glucosinolates on liver, muscle and distal kidney in parasite-free and salmon louse infected Atlantic salmon.
abstract: Reduction of Lepeophtheirus salmonis infection in Atlantic salmon achieved by glucosinolates (GLs) from Brassica plants was recently reported. However, wider application of functional feeds based on GLs requires better knowledge of their positive and adverse effects.
  
  
  
  Liver, distal kidney and muscle transcriptomes of salmon exposed to the extreme dose of GLs were profiled by microarray, while qPCR analysis followed up selected hepatic and renal responses under the extreme and moderate GLs dose during the L. salmonis challenge. Transcriptional analysis were complemented with measurements of organ indices, liver steatosis and plasma profiling, including indicators of cytolysis and bilirubin. Finally, the third trial was performed to quantify the effect of lower GLs doses on growth.
  
  
  
  The extreme GLs dose caused a decrease in hepatic fat deposition and growth, in line with microarray findings, which suggested tissue remodeling and reduction of cellular proliferation in the skeletal muscle and liver. Lower GLs inclusion levels in a follow-up trial did not show negative effects on growth. Microarray analysis of the distal kidney pointed to activation of anti-fibrotic responses under the overexposure. However, analyses of ALT, CK and AST enzymes in plasma provided no evidence of increased cytolysis and organ damage. Prevalent activation of phase-2 detoxification genes that occurred in all three tissues could be considered part of beneficial effects caused by the extreme dose of GLs. In addition, transcriptomic evidence suggested GLs-mediated iron and heme withdrawal response, including increased heme degradation in muscle (upregulation of heme oxygenase-1), decrease of its synthesis in liver (downregulation of porphobilinogen deaminase) and increased iron sequestration from blood (hepatic induction of hepcidin-1 and renal induction of intracellular storage protein ferritin). This response could be advantageous for salmon upon encountering lice, which depend on the host for the provision of iron carrying heme. Most of the hepatic genes studied by qPCR showed similar expression levels in fish exposed to GLs, lice and their combination, while renal induction of leptin suggested heightened stress by the combination of extreme dose of GLs and lice. High expression of interferon γ (cytokine considered organ-protective in mammalian kidney) was detected at the moderate GLs level. This fish also showed highest plasma bilirubin levels (degradation product of heme), and had lowest number of attached lice, further supporting hypothesis that making heme unavailable to lice could be part of an effective anti-parasitic strategy.
  
  
  
  Modulation of detoxification and iron metabolism in Atlantic salmon tissues could be beneficial prior and during lice infestations. Investigation of anti-lice functional feeds based on low and moderate GLs inclusion levels thus deserves further attention.
authors.affiliation: Cargill Innovation Center, Sea Lice Research Centre, Oslo, Norway. Stanko_Skugor@cargill.com.
authors.forename: Stanko
authors.initials: S
authors.lastname: Skugor
authors.affiliation: Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Sea Lice Research Centre, Oslo, Norway.
authors.forename: Helle
authors.initials: H
authors.lastname: Jodaa Holm
authors.affiliation: Cargill Innovation Center, Dirdal, Norway.
authors.forename: Anne Kari
authors.initials: AK
authors.lastname: Bjelland
authors.affiliation: Cargill Innovation Center, Puerto Montt, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pino
authors.affiliation: Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Sea Lice Research Centre, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Evensen
authors.affiliation: Nofima AS, Ås, Norway.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Krasnov
authors.affiliation: Cargill Innovation Center, Puerto Montt, Chile.
authors.forename: Simon
authors.initials: S
authors.lastname: Wadsworth
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D033342:Copepoda / Q000254:growth & development; D004478:Ectoparasitic Infestations / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary; D005393:Fish Diseases / Q000188:drug therapy* / Q000469:parasitology; D020869:Gene Expression Profiling; D005961:Glucosinolates / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D046228:Microarray Analysis; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D054647:Nutrigenomics; D060888:Real-Time Polymerase Chain Reaction; D020317:Salmo salar
chemical_list: D000977:Antiparasitic Agents; D005961:Glucosinolates
keywords: Antioxidant; Atlantic salmon; Detoxification; Functional feeds; Glucosinolates; Iron; Lepeophtheirus salmonis; Salmo salar; Salmon louse