title: High dietary lipid level is associated with persistent hyperglycaemia and downregulation of muscle Akt-mTOR pathway in Senegalese sole (Solea senegalensis).
abstract: High levels of dietary lipids are incorporated in feeds for most teleost fish to promote growth and reduce nitrogen waste. However, in Senegalese sole (Solea senegalensis) previous studies revealed that increasing the level of dietary lipids above 8% negatively affect growth and nutrient utilization regardless of dietary protein content. It has been shown that glucose regulation and metabolism can be impaired by high dietary fat intake in mammals, but information in teleost fish is scarce. The aim of this study was to assess the possible effect of dietary lipids on glucose metabolism in Senegalese sole with special emphasis on the regulation of proteins involved in the muscle insulin-signalling pathway. Senegalese sole juveniles (29 g) were fed two isonitrogenous diets (53% dry matter) for 88 days. These two diets were one with a high lipid level (∼17%, HL) and a moderate starch content (∼14%, LC), and the other being devoid of fish oil (4% lipid, LL) and with high starch content (∼23%, HC). Surprisingly, feeding Senegalese sole the HL/LC diet resulted in prolonged hyperglycaemia, while fish fed on LL/HC diet restored basal glycaemia 2 h after feeding. The hyperglycaemic phenotype was associated with greater glucose-6-phosphatase activity (a key enzyme of hepatic glucose production) and lower citrate synthase activity in the liver, with significantly higher liver glycogen content. Sole fed on HL/LC diet also had significantly lower hexokinase activity in muscle, although hexokinase activity was low with both dietary treatments. The HL/LC diet was associated with significant reductions in muscle AKT, p70 ribosomal S6-K1 Kinase (S6K-1) and ribosomal protein S6 (S6) 2 h after feeding, suggesting down regulation of the AKT-mTOR nutrient signalling pathway in these fish. The results of this study show for the first time that high level of dietary lipids strongly affects glucose metabolism in Senegalese sole.
authors.affiliation: CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental and ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal; INRA-UR 1067 Nutrition Métabolisme Aquaculture, Pôle Hydrobiologie, Saint Pée-sur-Nivelle, France.
authors.forename: Pedro
authors.initials: P
authors.lastname: Borges
authors.affiliation: CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental and ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Luísa M P
authors.initials: LM
authors.lastname: Valente
authors.affiliation: INRA-UR 1067 Nutrition Métabolisme Aquaculture, Pôle Hydrobiologie, Saint Pée-sur-Nivelle, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Véron
authors.affiliation: INRA-UR 1067 Nutrition Métabolisme Aquaculture, Pôle Hydrobiologie, Saint Pée-sur-Nivelle, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Dias
authors.affiliation: INRA-UR 1067 Nutrition Métabolisme Aquaculture, Pôle Hydrobiologie, Saint Pée-sur-Nivelle, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Panserat
authors.affiliation: INRA-UR 1067 Nutrition Métabolisme Aquaculture, Pôle Hydrobiologie, Saint Pée-sur-Nivelle, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Médale
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005412:Flatfishes; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D009124:Muscle Proteins; D038601:Ribosomal Protein S6; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1