Journal of Comparative Physiology B

, Volume 185, Issue 4, pp 413–423 | Cite as

Metabolic response in liver and Brockmann bodies of rainbow trout to inhibition of lipolysis; possible involvement of the hypothalamus–pituitary–interrenal (HPI) axis

  • Marta Librán-Pérez
  • Cristina Velasco
  • Cristina Otero-Rodiño
  • Marcos A. López-Patiño
  • Jesús M. Míguez
  • José L. Soengas
Original Paper


We previously demonstrated in rainbow trout that the decrease in circulating levels of fatty acid (FA) induced by treating fish with SDZ WAG 994 (SDZ) induced a counter-regulatory response in which the activation of the hypothalamus–pituitary–interrenal (HPI, equivalent to mammalian hypothalamus–pituitary–adrenal) axis was likely involved. This activation, probably not related to the control of food intake through FA sensor systems but to the modulation of lipolysis in peripheral tissues, liver and Brockmann bodies (BB, the main site of pancreatic endocrine cells in fish), would target the restoration of FA levels in plasma. To assess this hypothesis, we lowered circulating FA levels by treating fish with SDZ alone, or SDZ in the presence of metyrapone (an inhibitor of cortisol synthesis). In liver, the changes observed were not compatible with a direct FA-sensing response but with a stress response, which allows us to suggest that the detection of a FA decrease in the hypothalamus elicits a counter-regulatory response in liver, resulting in an activation of lipolysis to restore FA levels in plasma. The activation of these metabolic changes in liver could be attributable to the activation of the HPI axis and/or to the action of sympathetic pathways. In contrast, in BB, changes in circulating FA levels induce changes in several parameters compatible with the function of FA-sensing systems informing about the decrease in circulating FA levels.


Rainbow trout Fatty acid sensing Liver Brockmann bodies 



This study was supported by a research grant from Ministerio de Economía y Competitividad and European Fund for Regional Development (AGL2013-46448-C3-1-R and FEDER). M.L.-P. and C.O.-R were recipient of predoctoral fellowships (BES-2011-043394 and BES-2014-068040, respectively) from Ministerio de Economía y Competitividad.


  1. Alvarez MJ, Díez M, López-Bote C, Gallego M, Bautista JM (2000) Short-term modulation of lipogenesis by macronutrients in rainbow trout (Oncorhynchus mykiss) hepatocytes. Br J Nutr 84:619–628PubMedGoogle Scholar
  2. Barma P, Dey D, Basu D, Roy SS, Bhattacharya S (2006) Nutritionally induced insulin resistance in an Indian perch: a possible model for type 2 diabetes. Curr Sci 90:188–194Google Scholar
  3. Bernier NJ (2006) The corticotropin-releasing factor system as a mediator of the appetite-suppressing effects of stress in fish. Gen Comp Endocrinol 146:45–55CrossRefPubMedGoogle Scholar
  4. Bernier NJ, Peter RE (2001) Appetite-suppressing effects of urotensin I and corticotropin-releasing hormone in Goldfish (Carassius auratus). Neuroendocrinology 73:248–260CrossRefPubMedGoogle Scholar
  5. Blouet C, Schwartz GJ (2010) Hypothalamic nutrient sensing in the control of energy homeostasis. Behav Brain Res 209:1–12CrossRefPubMedGoogle Scholar
  6. Burnstock G (1959) The innervation of the gut of the brown trout Salmo trutta. Q J Microsc Sci 100:199–220Google Scholar
  7. Caspi L, Wang PYT, Lam TKT (2007) A balance of lipid-sensing mechanisms in the brain and liver. Cell Metab 6:99–104CrossRefPubMedGoogle Scholar
  8. Conde-Sieira M, Alvarez R, López-Patiño MA, Míguez JM, Flik G, Soengas JL (2013) ACTH-stimulated cortisol release from head kidney of rainbow trout is modulated by glucose concentration. J Exp Biol 216:554–567CrossRefPubMedGoogle Scholar
  9. Cox BF, Perrone MH, Welzel GE, Greenland BD, Colussi DJ, Merkel LA (1997) Cardiovascular and metabolic effects of adenosine A1-receptor agonists in streptozotocin-treated rats. J Cardiovasc Pharmacol 29:417–426CrossRefPubMedGoogle Scholar
  10. Cruz-Garcia L, Minghetti M, Navarro I, Tocher DR (2009) Molecular cloning, tissue expression and regulation of liver X receptor (LXR) transcription factors of Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol B 153:81–88CrossRefPubMedGoogle Scholar
  11. Diano S, Horvath TL (2012) Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends Mol Med 18:52–58CrossRefPubMedGoogle Scholar
  12. Dindia L, Faught E, Leonenko Z, Thomas R, Vijayan MM (2013) Rapid cortisol signaling in response to acute stress involves changes in plasma membrane order in rainbow trout liver. Am J Physiol Endocrinol Metab 304:E1157–E1166CrossRefPubMedGoogle Scholar
  13. Ditlecadet D, Driedzic WR (2012) Glycerol-3-phosphatase and not lipid recycling is the primary pathway in the accumulation of high concentrations of glycerol in rainbow smelt (Osmerus mordax). Am J Physiol Regul Integr Comp Physiol 304:R304–R312CrossRefPubMedGoogle Scholar
  14. Ducasse-Cabanot S, Zambonino-Infante J, Richard N, Medale F, Corraze G, Mambrini M, Robin J, Cahu C, Kaushik S, Panserat S (2007) Reduced lipid intake leads to changes in digestive enzymes in the intestine but has minor effects on key enzymes of hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss). Animal 1:1272–1282CrossRefPubMedGoogle Scholar
  15. Fabbri E, Capuzzo A, Moon TW (1998) The role of circulating catecholamines in the regulation of fish metabolism: an overview. Comp Biochem Physiol C 120:177–192PubMedGoogle Scholar
  16. Figueiredo-Silva AC, Kaushik S, Terrier F, Schrama JW, Médale F, Geurden I (2012) Link between lipid metabolism and voluntary food intake in rainbow trout fed coconut oil rich in medium-chain TAG. Br J Nutr 107:1714–1725CrossRefPubMedGoogle Scholar
  17. Jacobson KA, Gao ZG (2006) Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 5:247–264CrossRefPubMedCentralPubMedGoogle Scholar
  18. Keppler D, Decker K (1974) Glycogen determination with amyloglucosidase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 1127–1131Google Scholar
  19. Kolditz C, Borthaire M, Richard N, Corraze G, Panserat S, Vachot C, Lefevre F, Médale F (2008) Liver and muscle metabolic changes induced by dietary energy content and genetic selection in rainbow trout (Oncorhynchus mykiss). Am J Physiol Regul Integr Comp Physiol 294:R1154–R1164CrossRefPubMedGoogle Scholar
  20. Lam TKT (2010) Neuronal regulation of homeostasis by nutrient sensing. Nature Med 16:392–395CrossRefPubMedGoogle Scholar
  21. Lansard M, Panserat S, Seiliez I, Polakof S, Plagnes-Juan E, Geurden I, Médale F, Kaushik S, Corraze G (2009) Hepatic protein kinase B (Akt)-target of rapamycin (TOR)-signalling pathways and intermediary metabolism in rainbow trout (Oncorhynchus mykiss) are not significantly affected by feeding plant-based diets. Br J Nutr 102:1564–1573CrossRefPubMedGoogle Scholar
  22. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE (2009) Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am J Physiol Regul Integr Comp Physiol 297:R655–R664CrossRefPubMedCentralPubMedGoogle Scholar
  23. Librán-Pérez M, Polakof S, López-Patiño MA, Míguez JM, Soengas JL (2012) Evidence of a metabolic fatty acid sensing system in the hypothalamus and Brockmann bodies of rainbow trout: implications in food intake regulation. Am J Physiol Regul Integr Comp Physiol 302:R1340–R1350CrossRefPubMedGoogle Scholar
  24. Librán-Pérez M, Figueiredo-Silva AC, Panserat S, Geurden I, Míguez JM, Polakof S, Soengas JL (2013a) Response of hepatic lipid and glucose metabolism to a mixture or single fatty acids: possible presence of fatty acid-sensing mechanisms. Comp Biochem Physiol A 164:241–248CrossRefGoogle Scholar
  25. Librán-Pérez M, López-Patiño MA, Míguez JM, Soengas JL (2013b) Oleic acid and octanoic acid sensing capacity in rainbow trout Oncorhynchus mykiss is direct in hypothalamus and Brockmann bodies. PLoS ONE 8:e59507CrossRefPubMedCentralPubMedGoogle Scholar
  26. Librán-Pérez M, López-Patiño MA, Míguez JM, Soengas JL (2013c) In vitro response of putative fatty acid-sensing systems in rainbow trout liver to increased levels of oleate or octanoate. Comp Biochem Physiol A 165:288–294CrossRefGoogle Scholar
  27. Librán-Pérez M, Otero-Rodiño C, López-Patiño MA, Míguez JM, Soengas JL (2014a) Central administration of oleate or octanoate activates hypothalamic fatty acid sensing and inhibits food intake in rainbow trout. Physiol Behav 129:272–279CrossRefPubMedGoogle Scholar
  28. Librán-Pérez M, Velasco C, López-Patiño MA, Míguez JM, Soengas JL (2014b) Counter-regulatory response to a fall in circulating fatty acid levels in rainbow trout. Involvement of the hypothalamus–pituitary–interrenal axis. PLoS ONE 9:e113291CrossRefPubMedCentralPubMedGoogle Scholar
  29. Librán-Pérez M, Otero-Rodiño C, López-Patiño MA, Míguez JM, Soengas JL (2015) Effects of intracerebroventricular treatment with oleate or octanoate on fatty acid metabolism in Brockmann bodies and liver of rainbow trout. Aquac Nutr. doi: 10.1111/anu.12158 Google Scholar
  30. López-Patiño MA, Hernández-Pérez J, Gesto M, Librán-Pérez M, Míguez JM, Soengas JL (2014) Short-term time course of liver metabolic response to acute handling stress in rainbow trout, Oncorhynchus mykiss. Comp Biochem Physiol A 168:40–49CrossRefGoogle Scholar
  31. MacDonald MJ, Dobrzyn A, Ntambi J, Stoker SW (2008) The role of rapid lipogenesis in insulin secretion: insulin secretagogues acutely alter lipid composition of INS-1 832/13 cells. Arch Biochem Biophys 470:153–162CrossRefPubMedCentralPubMedGoogle Scholar
  32. Martinez-Rubio L, Wadsworth S, González Vecino JL, Bell JG, Tocher DR (2013) Effect of dietary digestible energy content on expression of genes of lipid metabolism and LC-PUFA biosynthesis in liver of Atlantic salmon (Salmo salar L.). Aquaculture 384–387:94–103CrossRefGoogle Scholar
  33. Migrenne S, Cruciani-Guglielmacci C, Kang L, Wang R, Rouch C, Lefèvre A-L, Ktorza A, Routh VH, Levin BE, Magnan C (2006) Fatty acid signaling in the hypothalamus and the neural control of insulin secretion. Diabetes 55:139–144CrossRefGoogle Scholar
  34. Milligan CL (2003) A regulatory role for cortisol in muscle glycogen metabolism in rainbow trout Oncorhynchus mykiss Walbaum. J Exp Biol 206:3167–3173CrossRefPubMedGoogle Scholar
  35. Morales AE, García-Rejón L, de la Higuera M (1990) Influence of handling and/or anaesthesia on stress response in rainbow trout. Effects on liver primary metabolism. Comp Biochem Physiol A 95:87–93CrossRefGoogle Scholar
  36. Morgan K, Obici S, Rossetti L (2004) Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 279:31139–31148CrossRefPubMedGoogle Scholar
  37. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L (2002) Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51:271–275CrossRefPubMedGoogle Scholar
  38. Oh YT, Oh K-S, Kang I, Youn JH (2012) A fall in plasma free fatty acid (FFA) level activates the hypothalamic-pituitary-adrenal axis independent of plasma glucose: evidence for brain sensing of circulating FFA. Endocrinology 153:3587–3592CrossRefPubMedCentralPubMedGoogle Scholar
  39. Oh YT, Kim J, Kang I, Youn JH (2014) Regulation of hypothalamic-pituitary-adrenal axis by circulating free fatty acids in male wistar rats: role of individual free fatty acids. Endocrinology 155:923–931CrossRefPubMedCentralPubMedGoogle Scholar
  40. Panserat S, Médale F, Blin C, Brèque J, Vachot C, Plagnes-Juan E, Gomes E, Krishnamoorthy R, Kaushik S (2000) Hepatic glucokinase is induced by dietary carbohydrates in rainbow trout, gilhead seabream, and common carp. Am J Physiol Regul Integr Comp Physiol 278:R1164–R1170PubMedGoogle Scholar
  41. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45CrossRefPubMedCentralPubMedGoogle Scholar
  42. Polakof S, Míguez JM, Moon TW, Soengas JL (2007a) Evidence for the presence of a glucosensor in hypothalamus, hindbrain, and Brockmann bodies of rainbow trout. Am J Physiol Regul Integr Comp Physiol 292:R1657–R1666CrossRefPubMedGoogle Scholar
  43. Polakof S, Míguez JM, Soengas JL (2007b) In vitro evidences for glucosensing capacity and mechanisms in hypothalamus, hindbrain, and Brockmann bodies of rainbow trout. Am J Physiol Regul Integr Comp Physiol 293:R1410–R1420CrossRefPubMedGoogle Scholar
  44. Polakof S, Míguez JM, Soengas JL (2008a) Changes in food intake and glucosensing function of hypothalamus and hindbrain in rainbow trout subjected to hyperglycemic or hypoglycemic conditions. J Comp Physiol A 194:829–839CrossRefGoogle Scholar
  45. Polakof S, Panserat S, Plagnes-Juan E, Soengas JL (2008b) Altered dietary carbohydrates significantly affect gene expression of the major glucosensing components in Brockmannn bodies and hypothalamus of rainbow trout. Am J Physiol Regul Integr Comp Physiol 295:R1077–R1088CrossRefPubMedGoogle Scholar
  46. Polakof S, Míguez JM, Soengas JL (2008c) Dietary carbohydrates induce changes in glucosensing capacity and food intake in rainbow trout. Am J Physiol Regul Integr Comp Physiol 295:R478–R489CrossRefPubMedGoogle Scholar
  47. Polakof S, Médale F, Skiba-Cassy S, Corraze G, Panserat S (2010) Molecular regulation of lipid metabolism in liver and muscle of rainbow trout subjected to acute and chronic insulin treatments. Domest Anim Endocrinol 39:26–33CrossRefPubMedGoogle Scholar
  48. Polakof S, Médale F, Larroquet L, Vachot C, Corraze G, Panserat S (2011) Insulin stimulates lipogenesis and attenuates beta-oxidation in white adipose tissue of fed rainbow trout. Lipids 46:189–199CrossRefPubMedGoogle Scholar
  49. Reid SD, Bernier NJ, Perry SF (1998) The adrenergic stress response in fish: control of catecholamine storage and release. Comp Biochem Physiol C 120:1–27PubMedGoogle Scholar
  50. Reubush KJ, Heath AG (1996) Metabolic responses to acute handling by fingerling inland and anadromous striped bass. J Fish Biol 49:830–841CrossRefGoogle Scholar
  51. Schwalme K, Mckay WC (1991) Mechanisms that elevate the glucose concentration of muscle and liver in yellow perch (Perca flavescens Mitchill) after exercise-handing stress. Can J Zool 69:456–461CrossRefGoogle Scholar
  52. Seth H, Axelsson M (2010) Sympathetic, parasympathetic and enteric regulation of the gastrointestinal vasculature in rainbow trout (Oncorhynchus mykiss) under normal and postprandial conditions. J Exp Biol 213:3118–3126CrossRefPubMedGoogle Scholar
  53. Soengas JL (2014) Contribution of glucose- and fatty acid sensing systems to the regulation of food intake in fish. A review. Gen Comp Endocrinol 205:36–48CrossRefPubMedGoogle Scholar
  54. Tripathi G, Verma P (2003) Pathway-specific response to cortisol in the metabolism of catfish. Comp Biochem Physiol B 136:463–471CrossRefPubMedGoogle Scholar
  55. Vijayan MM, Moon TW (1992) Acute handling stress alters hepatic glycogen metabolism in food-deprived rainbow trout (Oncorhynchus mykiss). Can J Fish Aquat Sci 49:2260–2266CrossRefGoogle Scholar
  56. Vijayan MM, Ballantyne JS, Leatherland JF (1990) High stocking density alters the energy metabolism of brook charr, Salvelinus fontinalis. Aquaculture 88:371–381CrossRefGoogle Scholar
  57. Wendelaar Bonga SE (1997) The stress response in fish. Physiol Rev 77:591–625PubMedGoogle Scholar
  58. Zhou D, Yuen P, Chu D, Thon V, McConnell S, Brown S, Tsang A, Pena M, Russell A, Cheng J-F, Nadzan AM, Barbosa MS, Dyck JRB, Lopaschuk GD, Yang G (2011) Expression, purification, and characterization of human malonyl-CoA decarboxylase. Prot Express Purif 34:261–269CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Marta Librán-Pérez
    • 1
  • Cristina Velasco
    • 1
  • Cristina Otero-Rodiño
    • 1
  • Marcos A. López-Patiño
    • 1
  • Jesús M. Míguez
    • 1
  • José L. Soengas
    • 1
  1. 1.Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Edificio de Ciencias ExperimentaisUniversidade de VigoVigoSpain

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