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Title: The administration of chitosan-tripolyphosphate-DNA nanoparticles to express exogenous SREBP1a enhances conversion of dietary carbohydrates into lipids in the liver of Sparus aurata
Author: Silva-Marrero, Jonás I.
Villasante, Juliana
Rashidpour, Ania
Palma, Mariana
Fábregas, A. (Anna)
Almajano Pablos, Ma. Pilar (María Pilar)
Viegas, Iván
Jones, John G.
Miñarro Carmona, Montserrat
Ticó Grau, Josep R.
Baanante, Isabel V.
Metón Teijeiro, Isidoro
Keywords: Quitosan
Metabolisme dels glúcids
Carbohydrate metabolism
Sparus aurata
Issue Date: 24-Jul-2019
Publisher: MDPI
Abstract: 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.
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It is part of: Biomolecules, 2019, vol. 9, p. 297
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ISSN: 2218-273X
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

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