title: Post-prandial regulation of hepatic glucokinase and lipogenesis requires the activation of TORC1 signalling in rainbow trout (Oncorhynchus mykiss).
abstract: To assess the potential involvement of TORC1 (target of rapamycin complex 1) signalling in the regulation of post-prandial hepatic lipid and glucose metabolism-related gene expression in trout, we employed intraperitoneal administration of rapamycin to achieve an acute inhibition of the TOR pathway. Our results reveal that rapamycin inhibits the phosphorylation of TORC1 and its downstream effectors (S6K1, S6 and 4E-BP1), without affecting Akt and the Akt substrates Forkhead-box Class O1 (FoxO1) and glycogen synthase kinase 3α/β (GSK 3α/β). These results indicate that acute administration of rapamycin in trout leads to the inhibition of TORC1 activation. No effect is observed on the expression of genes involved in gluconeogenesis, glycolysis and fatty acid oxidation, but hepatic TORC1 inhibition results in decreased sterol regulatory element binding protein 1c (SREBP1c) gene expression and suppressed fatty acid synthase (FAS) and glucokinase (GK) at gene expression and activity levels, indicating that FAS and GK activity is controlled at a transcriptional level in a TORC1-dependent manner. This study demonstrates for the first time in fish that post-prandial regulation of hepatic lipogenesis and glucokinase in rainbow trout requires the activation of TORC1 signalling.
authors.affiliation: INRA, UR 1067 Nutrition, Metabolism, Aquaculture, Aquapôle, CD 918, F-64310 Saint-Pée-sur-Nivelle, France.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Dai
authors.forename: Stéphane
authors.initials: S
authors.lastname: Panserat
authors.forename: Jan A
authors.initials: JA
authors.lastname: Mennigen
authors.forename: Frédéric
authors.initials: F
authors.lastname: Terrier
authors.forename: Karine
authors.initials: K
authors.lastname: Dias
authors.forename: Iban
authors.initials: I
authors.lastname: Seiliez
authors.forename: Sandrine
authors.initials: S
authors.lastname: Skiba-Cassy
mesh_terms: D000818:Animals; D005941:Glucokinase / Q000378:metabolism*; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010766:Phosphorylation; D019518:Postprandial Period; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D005941:Glucokinase; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: TORC1; fatty acid synthesis; gene expression; glycolysis; rainbow trout; rapamycin