title: Lysine and Leucine Deficiencies Affect Myocytes Development and IGF Signaling in Gilthead Sea Bream (Sparus aurata).
abstract: Optimizing aquaculture production requires better knowledge of growth regulation and improvement in diet formulation. A great effort has been made to replace fish meal for plant protein sources in aquafeeds, making necessary the supplementation of such diets with crystalline amino acids (AA) to cover the nutritional requirements of each species. Lysine and Leucine are limiting essential AA in fish, and it has been demonstrated that supplementation with them improves growth in different species. However, the specific effects of AA deficiencies in myogenesis are completely unknown and have only been studied at the level of hepatic metabolism. It is well-known that the TOR pathway integrates the nutritional and hormonal signals to regulate protein synthesis and cell proliferation, to finally control muscle growth, a process also coordinated by the expression of myogenic regulatory factors (MRFs). This study aimed to provide new information on the impact of Lysine and Leucine deficiencies in gilthead sea bream cultured myocytes examining their development and the response of insulin-like growth factors (IGFs), MRFs, as well as key molecules involved in muscle growth regulation like TOR. Leucine deficiency did not cause significant differences in most of the molecules analyzed, whereas Lysine deficiency appeared crucial in IGFs regulation, decreasing significantly IGF-I, IGF-II and IGF-IRb mRNA levels. This treatment also down-regulated the gene expression of different MRFs, including Myf5, Myogenin and MyoD2. These changes were also corroborated by a significant decrease in proliferation and differentiation markers in the Lysine-deficient treatment. Moreover, both Lysine and Leucine limitation induced a significant down-regulation in FOXO3 gene expression, which deserves further investigation. We believe that these results will be relevant for the production of a species as appreciated for human consumption as it is gilthead sea bream and demonstrates the importance of an adequate level of Lysine in fishmeal diet formulation for optimum growth.
authors.affiliation: Department of Fisheries Sciences, Faculty of Natural Resources, University of Tehran, Karaj, Iran.|Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Sheida
authors.initials: S
authors.lastname: Azizi
authors.affiliation: Department of Fisheries Sciences, Faculty of Natural Resources, University of Tehran, Karaj, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Nematollahi
authors.affiliation: Department of Fisheries Sciences, Faculty of Natural Resources, University of Tehran, Karaj, Iran.
authors.forename: Bagher
authors.initials: B
authors.lastname: Mojazi Amiri
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Vélez
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Esmail
authors.initials: E
authors.lastname: Lutfi
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Navarro
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Capilla
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gutiérrez
mesh_terms: D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007930:Leucine / Q000172:deficiency*; D008239:Lysine / Q000172:deficiency*; D032342:Muscle Cells / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D021541:Sea Bream / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018006:Myogenic Regulatory Factors; D007334:Insulin-Like Growth Factor I; D007930:Leucine; D008239:Lysine