Fish Physiology and Biochemistry

, Volume 44, Issue 2, pp 703–716 | Cite as

Effects of tetradecylthioacetic acid (TTA) treatment on lipid metabolism in salmon hearts—in vitro and in vivo studies

  • Regin Arge
  • Jens-Erik Dessen
  • Tone-Kari Østbye
  • Bente Ruyter
  • Magny S. Thomassen
  • Kjell-Arne Rørvik


In intensive farming of Atlantic salmon, a large proportion of observed mortality is related to cardiovascular diseases and circulatory failure, indicating insufficient robustness and inadequate cardiac performance. This paper reports on the use of tetradecylthioacetic acid (TTA) where the main objective was to enhance utilisation of fatty acids (FA), considered the main energy source of the heart. In this study, three experiments were conducted: (I) an in vivo study where salmon post-smolt were administrated dietary TTA in sea, (II) an in vitro study where isolated salmon heart cells were pre-stimulated with increasing doses of TTA and (III) an in vivo experiment where salmon post-smolt were subjected to injections with increasing doses of TTA. In study I, TTA-treated fish had a smaller decrease in heart weight relative to fish bodyweight (CSI) in a period after sea transfer compared to the control. This coincided with lowered condition factor and muscle fat in the TTA-treated fish, which may indicate a higher oxidation of lipids for energy. In study II, the isolated hearts treated with the highest dose of TTA had higher uptake of radiolabelled FA and formation of CO2 and acid-soluble products. In study III, expression of genes regulating peroxisomal FA oxidation, cell growth, elongation and desaturation were upregulated in the heart of TTA injected salmon. In contrast, genes involved in FA transport into the mitochondria were not influenced. In conclusion, these experiments indicate that TTA enhances energy production in salmon hearts by stimulation of FA oxidation.


Atlantic salmon Heart Fatty acid metabolism TTA 


Compliance with ethical standards

Ethical concern

The in vivo study I and the in vitro study were done in Norway and conducted according to the regulations for fish welfare set by the Norwegian Experimental Animal Authority. In the Faroe Islands, however, there is no legislation concerning experiments with animals, so the local “animal protection act” was adhered to throughout the in vivo II study (Vinnumálaráðið 1990). A fish veterinarian advised on best practice in relation to anaesthetization and injection procedures to ensure no undue suffering of the fish. There was no fish mortality caused by experimental procedures or management practice as effort was put into providing optimal welfare of the fish.


  1. Alne H, Thomassen MS, Takle H, Terjesen BF, Grammes F, Oehme M, Refstie S, Sigholt T, Berge RK, Rørvik K-A (2009) Increased survival by feeding tetradecylthioacetic acid during a natural outbreak of heart and skeletal muscle inflammation in S0 Atlantic salmon, Salmo salar L. J Fish Dis 32(11):953–961. CrossRefPubMedGoogle Scholar
  2. Arge R, Thomassen MS, Berge RK, Zambonino-Infante JL, Terjesen BF, Oehme M, Rørvik K-A (2012) Reduction of early sexual maturation in male S0 Atlantic salmon (Salmo salar L.) by dietary supplementation of tetradecylthioacetic acid (TTA). Aquac Res 45(5):1–12. Google Scholar
  3. Berge RK, Aarsland A, Kryvi H, Bremer J, Aarsaether N (1989) Alkylthio acetic acids (3-thia fatty acids)—a new group of non-β-oxidizable peroxisome-inducing fatty acid analogues—II. Dose-response studies on hepatic peroxisomal- and mitochondrial changes and long-chain fatty acid metabolizing enzymes in rats. Biochem Pharmacol 28:3969–3979CrossRefGoogle Scholar
  4. Berge RK, Skorve J, Tronstad KJ, Berge K, Gudbrandsen OA, Grav H (2002) Metabolic effects of thia fatty acids. Curr Opin Lipidol 13(3):295–304. CrossRefPubMedGoogle Scholar
  5. Bremer J (2001) Review: the biochemistry of hypo- and hyperlipidemic fatty acid derivatives: metabolism and metabolic effects. Prog Lipid Res 40(4):231–268. CrossRefPubMedGoogle Scholar
  6. Brocklebank J, Raverty S (2002) Sudden mortality caused by cardiac deformities following seining of preharvest farmed Atlantic salmon (Salmo salar) and by cardiomyopathy of postintraperitoneally vaccinated Atlantic salmon parr in British Columbia. Can Vet J 43(2):129–130PubMedPubMedCentralGoogle Scholar
  7. Castro V, Grisdale-Helland B, Helland SJ, Kristensen T, Jørgensen SM, Helgerud J, Claireaux G, Farrell AP, Krasnov A, Takle H (2011) Aerobic training stimulates growth and promotes disease resistance in Atlantic salmon (Salmo salar). Comp Biochem Physiol 160(2):278–290. CrossRefGoogle Scholar
  8. Castro V, Grisdale-Helland B, Helland SJ, Torgersen J, Kristensen T, Claireaux G (2013) Cardiac molecular-acclimation mechanisms in response to swimming-induced exercise in Atlantic salmon. PLoS One 8(1):e55056. CrossRefPubMedPubMedCentralGoogle Scholar
  9. Christiansen R, Borrebaek B, Bremer J (1976) The effect of (−)carnitine on the metabolism of palmitate in liver cells isolated from fasted and refed rats. FEBS Lett 62(3):313–317. CrossRefPubMedGoogle Scholar
  10. Dannevig BH, Berg T (1985) Endocytosis of galactose-terminated glycoproteins by isolated liver cells of the rainbow trout (Salmo gairdneri). Comp Biochem Physiol B Comp Biochem 82(4):683–688. CrossRefGoogle Scholar
  11. Dessen J-E, Arge R, Thomassen MS, Rørvik K-A (2016) Differences in fat accumulation between immature male and female Atlantic salmon Salmo salar after dietary administration of tetradecylthioacetic acid. J Fish Biol 89(4):2085–2097. CrossRefPubMedGoogle Scholar
  12. Folch J, Lees M, Sloane Stanley GH (1957) Simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–507PubMedGoogle Scholar
  13. Gilde AJ, van der Lee KAJM, Willemsen PHM, Chinetti G, van der Leij FR, van der Vusse GJ, Staels B, van Bilsen M (2003) Peroxisome proliferator-activated receptor (PPAR) α and PPAR β/δ, but not PPARγ, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92:518–524. CrossRefPubMedGoogle Scholar
  14. Grammes F, Rørvik K-A, Takle H (2012a) Tetradecylthioacetic acid modulates cardiac transcription in Atlantic salmon, Salmo salar L., suffering heart and skeletal muscle inflammation. J Fish Dis 35(2):109–117. CrossRefPubMedGoogle Scholar
  15. Grammes F, Rørvik K-A, Thomassen MS, Berge RK, Takle H (2012b) Genome wide response to dietary tetradecylthioacetic acid supplementation in the heart of Atlantic salmon (Salmo salar L.) BMC Genomics 13(1):180. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hardie DG (2004) AMP-activated protein kinase: a master switch in glucose and lipid metabolism. Rev Endocr Metab Disord 5(2):119–125. CrossRefPubMedGoogle Scholar
  17. Hjeltnes B, Samuelsen OB, Svardal AM (1992) Changes in plasma and liver glutathione levels in Atlantic salmon Salmo salar suffering from infectious salmon anemia (ISA). Dis Aquat Org 14:31–33. CrossRefGoogle Scholar
  18. Hvattum E, Grav HJ, Bremer J (1993) Hormonal and substrate regulation of 3-thia fatty acid metabolism in Morris 7800 C1 hepatoma cells. Biochem J 294(3):917–921. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Jäger S, Handschin C, Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1 alpha. P Natl Acad Sci USA 104(29):12017–12022. CrossRefGoogle Scholar
  20. Kleveland EJ, Ruyter B, Vegusdal A, Sundvold H, Berge RK, Gjøen T (2006) Effects of 3-thia fatty acids on expression of some lipid related genes in Atlantic salmon (Salmo salar L.) Comp Biochem Physiol Part B 145:239–248CrossRefGoogle Scholar
  21. Kennedy SR, Bickerdike R, Berge RK, Dick JR, Tocher DR (2007) Influence of conjugated linoleic acid (CLA) or tetradecylthioacetic acid (TTA) on growth, lipid composition, fatty acid metabolism and lipid gene expression of rainbow trout (Oncorhynchus mykiss L.) Aquaculture 272(1-4):489–501. CrossRefGoogle Scholar
  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMedGoogle Scholar
  23. McClelland GB, Dalziel AC, Fragoso NM, Moyes CD (2005) Muscle remodeling in relation to blood supply: implications for seasonal changes in mitochondrial enzymes. J Exp Biol 208(3):515–522. CrossRefPubMedGoogle Scholar
  24. Moya-Falcon C, Hvattum E, Dyrøy E, Skorve J, Stefansson SO, Thomassen MS, Jakobsen JV, Berge RK, Ruyter B (2004) Effects of 3-thia fatty acids on feed intake, growth, tissue fatty acid composition, β-oxidation and Na+,K+-ATPase activity in Atlantic salmon. Comp Biochem Physiol Part B 139:657–668CrossRefGoogle Scholar
  25. Moya-Falcón C, Hvattum E, Tran TN, Thomassen MS, Skorve J, Ruyter B (2006) Phospholipid molecular species, beta-oxidation, desaturation and elongation of fatty acids in Atlantic salmon hepatocytes: effects of temperature and 3-thia fatty acids. Comp Biochem Physiol Part B 145(1):68–80. CrossRefGoogle Scholar
  26. Moyes CD, Mathieu-Costello OA, Brill RW, Hochachka PW (1992) Mitochondrial metabolism of cardiac and skeletal muscles from a fast (Katsuwonus pelamis) and a slow (Cyprinus carpio) fish. Can J Zool 70(6):1246–1253. CrossRefGoogle Scholar
  27. Nurmi A, Vornanen M (2002) Electrophysiological properties of rainbow trout cardiac myocytes in serum-free primary culture. Am J Physiol Regulatory Integrative Comp Physiol 282:1200–1209CrossRefGoogle Scholar
  28. Patton S, Zulak IM, Trams EG (1975) Fatty acid metabolism via triglyceride in the salmon heart. J Mol Cell Cardiol 7(11):857–865. CrossRefPubMedGoogle Scholar
  29. Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83(2):346–356. CrossRefPubMedGoogle Scholar
  30. Polakof S, Panserat S, Craig PM, Martyres DJ, Plagnes-Juan E (2011) The metabolic consequences of hepatic AMP-kinase phosphorylation in rainbow trout. PLoS One 6(5):e20228. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Poppe TT, Johansen R, Gunnes G, Tørud B (2003) Heart morphology in wild and farmed Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss. Dis Aquat Org 57(1-2):103–108. CrossRefPubMedGoogle Scholar
  32. Poppe TT, Taksdal T (2000) Ventricular hypoplasia in farmed Atlantic salmon Salmo salar. Dis Aquat Org 42(1):35–40. CrossRefPubMedGoogle Scholar
  33. Rørvik K-A, Alne H, Gaarder M, Ruyter B, Måseide NP, Jakobsen JV, Berge RK, Sigholt T, Thomassen MS (2007) Does the capacity for energy utilization affect the survival of post-smolt Atlantic salmon, Salmo salar L., during natural outbreaks of infectious pancreatic necrosis? J Fish Dis 30(7):399–409. CrossRefPubMedGoogle Scholar
  34. Seglen PO (1976) Preparation of isolated rat liver cells. Methods Cell Biol 13:29–83. CrossRefPubMedGoogle Scholar
  35. Skrede S, Sørensen HN, Larsen LN, Steineger HH, Høvik K, Spydevold OS, Horn R, Bremer J (1997) Thia fatty acids, metabolism and metabolic effects. Biochim Biophys Acta 1344(2):115–131. CrossRefPubMedGoogle Scholar
  36. Schiller Vestergren A, Trattner S, Mráz J, Ruyter B, Pickova J (2011) Fatty acids and gene expression responses to bioactive compounds in Atlantic salmon (Salmo salar L.) hepatocytes. Neuroendocrinol Lett 32(Suppl. 2):41–50PubMedGoogle Scholar
  37. Schiller Vestergren A, Wagner L, Pickova J, Rosenlund G, Kamal-Eldin A, Trattner S (2012) Sesamin modulates gene expression without corresponding effect on fatty acids in Atlantic salmon (Salmo salar L.) Lipids 47(9):897–911. CrossRefPubMedGoogle Scholar
  38. Vinnumálaráðið (1990). Løgtingslóg nr. 9 frá 14. mars 1985 um vernd av dýrum, sum seinast broytt við løgtingslóg nr. 56 frá 19. mai 2015. Available at: (Last accessed May 2017)
  39. VKM (2014). Panel on animal health and welfare; risk assessment of amoebic gill disease, VKM Report 2014. Available online: Accessed 15 Jan 2018
  40. West TG, Arthur PG, Suarez RK, Doll CJ, Hochachka PW (1993) In vivo utilization of glucose by heart and locomotory muscles of exercising rainbow trout (Oncorhynchus mykiss). J Exp Biol 177:63–79Google Scholar
  41. Zhou M, Xu A, Tam PKH, Lam KSL, Huang B (2012) Upregulation of UCP2 by adiponectin: the involvement of mitochondrial superoxide and hnRNP K. PLoS One 7(2):e32349. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Animal and Aquacultural SciencesNorwegian University of Life SciencesÅsNorway
  2. 2.Formerly associated with Fiskaaling, Aquacultural Research Station of the FaroesHvalvíkFaroe Islands
  3. 3.Nofima ASÅsNorway

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