The administration of chitosan-tripolyphosphate-DNA nanoparticles to express exogenous SREBP1a enhances conversion of dietary carbohydrates into lipids in the liver of Sparus aurata
| Autor: | Isidoro Metón, Ania Rashidpour, Montserrat Miñarro, María Pilar Almajano, Anna Fàbregas, Mariana Palma, John G. Jones, Isabel V. Baanante, Jonás I. Silva-Marrero, Juliana Villasante, Ivan Viegas, Josep R. Ticó |
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| Přispěvatelé: | Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, Universitat Politècnica de Catalunya. CRESCA - Centre de Recerca en Seguretat i Control Alimentari, Universitat de Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genetic Vectors lcsh:QR1-502 Carbohydrate metabolism Metabolisme cel·lular Biochemistry Article lcsh:Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enginyeria química [Àrees temàtiques de la UPC] Sparus aurata Dietary Carbohydrates Animals Glycolysis Gene delivery gene delivery Molecular Biology Fatty acid synthesis Chitosan Nanopartícules biology Glucokinase Quitosan Lipogenesis Metabolisme dels glúcids Metabolism Sea Bream Orada Sterol regulatory element-binding protein 030104 developmental biology Fatty acid desaturase Liver chemistry 030220 oncology & carcinogenesis biology.protein Nanoparticles nanoparticles chitosan SREBP1 Sterol Regulatory Element Binding Protein 1 metabolism Plasmids |
| Zdroj: | UPCommons. Portal del coneixement obert de la UPC Universitat Politècnica de Catalunya (UPC) Biomolecules, Vol 9, Iss 8, p 297 (2019) Biomolecules Volume 9 Issue 8 Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona |
| Popis: | In addition to being essential for the transcription of genes involved in cellular lipogenesis, increasing evidence associates sterol regulatory element binding proteins (SREBPs) with the transcriptional control of carbohydrate metabolism. The aim of this study was to assess the effect of overexpression SREBP1a, a potent activator of all SREBP-responsive genes, on the intermediary metabolism of Sparus aurata, a glucose-intolerant carnivorous fish. Administration of chitosan-tripolyphosphate nanoparticles complexed with a plasmid driving expression of the N-terminal transactivation domain of SREBP1a significantly increased SREBP1a mRNA and protein in the liver of S. aurata. Overexpression of SREBP1a enhanced the hepatic expression of key genes in glycolysis-gluconeogenesis (glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase), fatty acid synthesis (acetyl-CoA carboxylase 1 and acetyl-CoA carboxylase 2), elongation (elongation of very long chain fatty acids protein 5) and desaturation (fatty acid desaturase 2) as well as reduced nicotinamide adenine dinucleotide phosphate production (glucose-6-phosphate 1-dehydrogenase) and cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase), leading to increased blood triglycerides and cholesterol levels. Beyond reporting the first study addressing in vivo effects of exogenous SREBP1a in a glucose-intolerant model, our findings support that SREBP1a overexpression caused multigenic effects that favoured hepatic glycolysis and lipogenesis and thus enabled protein sparing by improving dietary carbohydrate conversion into fatty acids and cholesterol. |
| Databáze: | OpenAIRE |
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