Genòmica funcional en peixos

Over the last 20 years, our research group has been pioneer in the molecular characterization of key enzymes involved in control of the intermediary metabolism in fish. Some relevant results include:

• Although over decades glucose intolerance in fish was attributed, at least in part, to lack of GK activity in the liver, we demonstrated functionality of Sparus aurata GK and that GK expression in the liver is largely dependent on nutritional status (Caseras et al., 2000, BBA-Gene Struct Expr 1493: 135-141).

• Identification of Sterol Regulatory Element Binding Protein 1 (SREBP1) as a key transcription factor that mediates postprandial up-regulation of glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in the liver of Sparus aurata (Metón et al., 2006, Endocrinology 147: 3446-3456; Egea et al., 2008, Gen Comp Endocrinol 155: 359-367).

• Demonstration that cytosolic alanine aminotransferase (cALT) gene generates two isoforms (cALT1 and cALT2) by alternative splicing in Sparus aurata (Anemaet et al., 2008, Int J Biochem Cell Biol 40: 2833-2844). Inhibition of cALT activity favours protein sparing through increased pyruvate kinase (PK) activity and decreased renewal rate of alanine in the liver of Sparus aurata (González et al., 2012, Br J Nutr 107: 1747-1756).

• First reports in animals for a mitochondrial ALT (mALT) protein sequence (Metón et al., 2004, FEBS Lett 566: 251-254), and for cALT and mALT gene promoters (Anemaet et al., 2010, J Mol Endocrinol 45: 119-132; Salgado et al., 2012, Mar Biotechnol 14: 46-62).

• Demonstration that Activating Transcription Factor 4 (ATF4) transactivates human ALT2 promoter under mitochondrial stress conditions (Salgado et al., 2014, BBA-Gene Regul Mech 1839: 288-296).

• Transcriptomic analysis: identification of new biomarkers involved in growth, nutritional status and mitochondrial oxidative phosphorylation in Sparus aurata (Silva-Marrero et al., 2017, BMC Genomics 18 (1): 768; Sáez-Arteaga et al., 2022, Aquaculture 738221, doi: 10.1016/j.aquaculture.2022.738221).

• Development of in vivo transient gene therapy through intraperitoneal administration of chitosan-tripolyphosphate (TPP) nanoparticles complexed with expression plasmids. Expression of a short hairpin RNA (shRNA) designed to knockdown cALT expression increases the activity of rate-limiting enzymes in glycolysis in the liver of Sparus aurata (González et al., 2016, Mar Biotechnol 18: 85-97), while silencing glutamate dehydrogenase expression decreases amino acid transdeamination and gluconeogenesis in the liver of Sparus aurata (Gaspar et al., 2018, J Biotechnol 286: 5-13).

• Transient therapy for multigenic effects in vivo: administration of chitosan-TPP-DNA nanoparticles to overexpress the transcription factor SREBP1a generates a multigenic effect in the liver of Sparus aurata, leading to increased expression of genes encoding key enzymes in glycolyis, fatty acid synthesis and colesterol synthesis, which in turn stimulates lipid biosynthesis from carbohydrates in glucose intolerant carnivorous fish (Silva-Marrero et al., 2019, Biomolecules 9 (8): E297).

• Transcriptional control of gene expression in vivo
• Functional genomics and intermediary metabolism in fish
• Fish transcriptomics and nutritional regulation of gene expression in fish

Title: Administración de nanopartículas de quitosano-DNA plasmídico para biosintetizar ácidos grasos poliinsaturados omega-3 y ahorrar proteína en Sparus aurata
Financing institution: Ministerio de Ciencia e Innovación (Spain)
Code of the project: PID2021-125642OB-I00
Principal Investigator: Isidoro Metón Teijeiro
Start and end dates: 01/09/2022 - 31/08/2025

Title: GRC d'Antioxidants en Agrobiotecnologia
Financing institution: Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR (Generalitat de Catalunya)
Code of the project: 2021 SGR 00675
Principal Investigator: Sergi Munné Bosch
Start and end dates: 01/01/2022 - 31/12/2024

Title: Control de la expresión génica para ahorrar proteína e incrementar la utilización de los carbohidratos de la dieta en la producción de dorada (Sparus aurata)
Financing institution: Ministerio de Economia y Competitividad (Spain)
Code of the project: AGL2016-78124-R
Principal Investigator: Isidoro Metón Teijeiro
Start and end dates: 30/12/2016 - 31/12/2020

Title: Biotecnologia vegetal: producció de fitofàrmacs 
Financing institution: Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR (Generalitat de Catalunya)
Code of the project: 2014SGR215
Principal Investigator: Javier Palazón Barandela
Start and end dates: 01/01/2014 - 31/12/2016

Title: Identificación y validación de genes biomarcadores para mejorar la producción de Sparus aurata mediante la optimización del uso de los nutrientes de la dieta
Financing institution: Ministerio de Economia y Competitividad (Spain)
Code of the project: AGL2012-33305
Principal Investigator: Isidoro Metón Teijeiro
Start and end dates: 01/01/2013 - 31/12/2015

Title: Optimizing carbohydrate utilization in farmed sea-bass through metabolic profiling
Financing institution: Ministério da Ciência, Tecnologia e Ensino Superior (Portugal)
Code of the project: PTDC/EBB-BIO/098111/2008
Principal Investigator: John Griffith Jones 
Start and end dates: 01/05/2010 - 30/04/2013

• Wu, Y.; Rashidpour, A.; Fàbregas, A.; Almajano, M.P.; Metón, I. Chitosan-based delivery of fish codon-optimised Caenorhabditis elegans FAT-1 and FAT-2 boosts EPA and DHA biosynthesis in Sparus aurata. Reviews in Fish Biology and Fisheries (2024) In press. doi: 10.1007/s11160-024-09852-4 Abstract

• Rashidpour, A.; Wu, Y.; Almajano, M.P.; Fàbregas, A.; Metón, I. Chitosan-based sustained expression of SREBP1a stimulates hepatic glucose oxidation and growth in Sparus aurata. Marine Drugs (2023) 21: 562. doi: 10.3390/md21110562 Abstract

• Ouerfelli, M.; Metón, I.; Codina-Torrella, I.; Almajano, M.P. Antibacterial and antiproliferative activities of Azadirachta indica leaf extract and its effect on oil-in-water food emulsion stability. Molecules (2022) 27: 7772. doi: 10.3390/molecules27227772 Abstract

• Ouerfelli, M.; Metón, I.; Codina-Torrella, I.; Almajano, M.P. Phenolic profile, EPR determination, and antiproliferative activity against human cancer cell lines of Anthyllis vulneraria extracts. Molecules (2022) 27: 7495. doi: 10.3390/molecules27217495 Abstract

• Sáez-Arteaga, A.; Wu, Y.; Silva-Marrero, J.I.; Rashidpour, A.; Almajano, M.P.; Fernández, F.; Baanante, I.V.; Metón, I. Gene markers of dietary macronutrient composition and growth in the skeletal muscle of gilthead sea bream (Sparus aurata). Aquaculture (2022) 555: 738221. doi: 10.1016/j.aquaculture.2022.738221 Abstract

• Villasante, J.; Espinosa-Ramírez, J.; Pérez-Carrillo, E.; Heredia-Olea, E.; Metón, I.; Almajano, M.P. Evaluation of non-extruded and extruded pecan (Carya illinoinensis) shell powder as functional ingredient in bread and wheat tortilla. LWT (2022) 160: 113299. Abstract

• Wu, Y.; Rashidpour, A.; Almajano, M.P.; Metón, I. Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology. Polymers (2020) 12 (5): 1177. Abstract

• Villasante, J.; Ouerfelli, M.; Bobet, A.; Metón, I.; Almajano, M.P. The Effects of Pecan Shell, Roselle Flower and Red Pepper on the Quality of Beef Patties during Chilled Storage. Foods (2020) 9 (11): 1692. Abstract

• Babaei, S.; Abedian-Kenari, A.; Naseri, M.; Yazdani-Sadati, M.A.; Metón, I. Impact of starvation on digestive enzymes activities and plasma metabolites in Siberian sturgeon (Acipenser baerii, Brandt, 1869). Aquaculture Research (2020) 51 (4): 1689-1699. Abstract

• Younus, N.; Zuberi, A.; Rashidpour, A.; Metón, I. Dietary cobalt supplementation improves growth and body composition and induces the expression of growth and stress response genes in Tor putitora. Fish Physiology and Biochemistry (2020) 46: 371-381. Abstract

• Silva-Marrero, J.I.; Villasante, J.; Rashidpour, A.; Palma, M.; Fàbregas, A.; Almajano, M.P.; Viegas, I.; Jones, J.G.; Miñarro, M.; Ticó, J.R.; Baanante, I.V.; Metón, I. The Administration of Chitosan-Tripolyphosphate-DNA Nanoparticles to Express Exogenous SREBP1a Enhances Conversion of Dietary Carbohydrates into Lipids in the Liver of Sparus aurata. Biomolecules (2019) 9 (8): E297. Abstract

• Villasante, J.; Pérez-Carrillo, E.; Heredia-Olea, E.; Metón, I.; Almajano, M.P. In Vitro Antioxidant Activity Optimization of Nut Shell (Carya illinoinensis) by Extrusion Using Response Surface Methods. Biomolecules (2019) 9 (12): E883. Abstract

• Khojasteh, A.; Metón, I.; Camino, S.; Cusido, R.M.; Eibl, R.; Palazon, J. In Vitro Study of the Anticancer Effects of Biotechnological Extracts of the Endangered Plant Species Satureja Khuzistanica. International Journal of Molecular Science (2019) 20 (10): E2400. Abstract

• Rashidpour, A.; Silva-Marrero, J.I.; Seguí, L.; Baanante, I.V.; Metón, I. Metformin counteracts glucose-dependent lipogenesis and impairs transdeamination in the liver of gilthead sea bream (Sparus aurata). American Journal of Physiology-Regulatory Integrative and Comparative Physiology (2019) 316 (3): R265-R273. Abstract

• Villasante, J.; Girbal, M.; Metón, I.; Almajano, M.P. Effects of Pecan Nut (Carya illinoiensis) and Roselle Flower (Hibiscus sabdariffa) as Antioxidant and Antimicrobial Agents for Sardines (Sardina pilchardus). Molecules (2019) 24 (1): 85. Abstract

• Rito, J.; Viegas, I.; Pardal, M.Â.; Metón, I.; Baanante, I.V.; Jones, J.G. Utilization of Glycerol for Endogenous Glucose and Glycogen Synthesis in Seabass (Dicentrarchus labrax): a Potential Mechanism for Sparing Amino Acid Catabolism in Carnivorous Fish. Aquaculture (2019) 498: 488-495. Abstract

• Rito, J; Viegas, I.; Pardal, M.A.; Metón, I.; Baanante, I.V.; Jones, J.G. Disposition of a Glucose Load into Hepatic Glycogen by Direct and Indirect Pathways in Juvenile Seabass and Seabream. Scientific Reports (2018) 8 (1): 464. Abstract

• Gaspar, C.; Silva-Marrero, J.I.; Salgado, M.C.; Baanante, I.V.; Metón, I. Role of upstream stimulatory factor 2 in glutamate dehydrogenase gene transcription. Journal of Molecular Endocrinology (2018) 60 (3) :247-259. Abstract

• Gaspar, C.; Silva-Marrero, J.I.; Fàbregas, A.; Miñarro, M.; Ticó, J.R.; Baanante, I.V.; Metón, I. Administration of chitosan-tripolyphosphate-DNA nanoparticles to knockdown glutamate dehydrogenase expression impairs transdeamination and gluconeogenesis in the liver. Journal of Biotechnology (2018) 286: 5-13. Abstract

• Silva-Marrero, J.I.; Sáez, A.; Caballero-Solares, A.; Viegas, I.; Almajano, M.P.; Fernández, F.; Baanante, I.V.; Metón, I. A transcriptomic approach to study the effect of long-term starvation and diet composition on the expression of mitochondrial oxidative phosphorylation genes in gilthead sea bream (Sparus aurata). BMC Genomics (2017) 18 (1): 768. Abstract

• Gallego, A.; Metón, I.; Baanante, I.V.; Ouazzani, J.; Adelin, E.; Palazon, J.; Bonfill, M.; Moyano, E. Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines. Biomedicine & Pharmacotherapy (2017) 89: 565-572. Abstract

• Babaei, S.; Sáez, A.; Caballero-Solares, A.; Fernández, F.; Baanante, I.V.; Metón, I. Effect of dietary macronutrients on the expression of cholecystokinin, leptin, ghrelin and neuropeptide Y in gilthead sea bream (Sparus aurata). General and Comparative Endocrinology (2017) 240: 121-128. Abstract

• Viegas, I.; Jarak, .I; Rito, J.; Carvalho, R.A.; Metón, I.; Pardal, M.A.; Baanante, I.V.; Jones, J.G. Effects of dietary carbohydrate on hepatic de novo lipogenesis in European seabass (Dicentrarchus labrax L.). Journal of Lipid Research (2016) 57: 1264-1272. Abstract

• Babaei, S.; Abedian Kenari, A.; Hedayati, M.; Yazdani Sadati, M.A.; Metón, I. Effect of diet composition on growth performance, hepatic metabolism and antioxidant activities in Siberian sturgeon (Acipenser baerii, Brandt, 1869) submitted to starvation and refeeding. Fish Physiology and Biochemistry (2016) 42 (6): 1509-1520. Abstract

• González, J.D.; Silva-Marrero, J.I.; Metón, I.; Caballero, A.; Viegas, I.; Fernández, F.; Miñarro, M.; Fàbregas, A.; Ticó, J.R.; Jones, J.G.; Baanante, I.V. Chitosan-mediated shRNA knockdown of cytosolic alanine aminotransferase improves hepatic carbohydrate metabolism. Marine Biotechnology (2016) 18: 85-97. Abstract

• Viegas, I.; Rito, J.; Jarak, I.; Leston, S.; Caballero-Solares, A.; Metón, I.; Pardal, M.A.; Baanante, I.V.; Jones, J.G. Contribution of dietary starch to hepatic and systemic carbohydrate fluxes in European seabass (Dicentrarchus labrax L.). British Journal of Nutrition (2015) 113: 1345-1354. Abstract

• Salgado, M.C.; Metón, I.; Anemaet, I.G.; Baanante, I.V. Activating transcription factor 4 mediates up-regulation of alanine aminotransferase 2 gene expression under metabolic stress. BBA - Gene Regulatory Mechanisms (2014) 1839: 288-296. Abstract

• Soares, A.F.; Carvalho, R.A.; Veiga, F.J.; Alves, M.G.; Martins, F.O.; Viegas, I.; González, J.D.; Metón, I.; Baanante, I.V.; Jones, J.G. Restoration of Direct Pathway Glycogen Synthesis Flux in the STZ-diabetes Rat Model by Insulin Administration. American Journal of Physiology-Endocrinology and Metabolism (2012) 303: E875-E885. Abstract

• Gonzalez, J.D.; Caballero, A.; Viegas, I.; Metón, I.; Jones, J.G.; Barra, J.; Fernández, F.; Baanante, I.V. Effects of alanine aminotransferase inhibition on the intermediary metabolism in Sparus aurata through dietary amino-oxyacetate supplementation. British Journal of Nutrition (2012)  107: 1747-1756. Abstract

• Salgado, M.C.; Metón, I.; Anemaet, I.G.; González, J.D.; Fernández, F.; Baanantea, I.V. Hepatocyte nuclear factor 4alpha transactivates the mitochondrial alanine aminotransferase gene in the kidney of Sparus aurata. Marine Biotechnology (2012) 14: 46-62. Abstract

• Anemaet, I.G.; González, J.D.; Salgado, M.C.; Giralt, M.; Fernández, F.; Baanante, I.V.; Metón, I. Transactivation of cytosolic alanine aminotransferase gene promoter by p300 and c-Myb. Journal of Molecular Endocrinology (2010) 45: 119-132. Abstract

• Anemaet, I.G.; Metón, I.; Salgado M.C.; Fernández, F.; Baanante, I.V. A novel alternatively spliced transcript of cytosolic alanine aminotransferase gene associated with enhanced gluconeogenesis in the liver of gilthead sea bream (Sparus aurata). International Journal of Biochemistry and Cell Biology (2008) 40: 2833-2844. Abstract

• Egea, M., Metón, I., Córdoba., M, Fernández, F., & Baanante, I.V. Role of Sp1 and SREBP-1a in the insulin-mediated regulation of glucokinase transcription in the liver of gilthead seabream (Sparus aurata). General and Comparative Endocrinology (2008) 155: 359-367. Abstract

• Egea, M., Metón, I., & Baanante, I.V. Sp1 and Sp3 regulate glucokinase gene transcription in the liver of gilthead sea bream (Sparus aurata). Journal of Molecular Endocrinology (2007) 38: 481-492. Abstract

• Metón, I., Egea, M., Anemaet, I.G., Fernández, F., & Baanante, I.V. Sterol Regulatory Element Binding Protein-1a Transactivates 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase Gene Promoter. Endocrinology (2006) 147: 3446-3456. Abstract

• Metón, I.; Egea, M.; Fernández, F.; Eraso, M.C.; Baanante, I.V. The N-terminal sequence directs import of mitochondrial alanine aminotransferase into mitochondria. FEBS Letters (2004) 566: 251-254. Abstract

• Caseras, A.; Metón, I.; Fernández, F.; Baanante, I.V. Glucokinase gene expression is nutritionally regulated in liver of gilthead sea bream (Sparus aurata). BBA - Gene Structure and Expression (2000) 1493: 135-141. Abstract

• Metón, I.; Mediavilla, D.; Caseras, A.; Cantó, E.; Fernández, F.; Baanante, I.V. Effect of diet composition and ration size on key enzyme activities of glycolysis-gluconeogenesis, the pentose phosphate pathway and amino acid metabolism in liver of gilthead sea bream (Sparus aurata). British Journal of Nutrition (1999) 82: 223-232. Abstract

• Transient gene therapy in vivo: chitosan-tripolyphosphate-DNA nanoparticles.
• Transcriptomic analysis by RNA-seq and DNA microarrays.
• Transcriptional activity of gene promoters. Electrophoretic mobility shift assay (EMSA). Chromatine immunoprecipitation  (ChIP).
• Quantitative real-time RT-PCR, RACE-PCR, DNA sequencing.
• Construction and screening of cDNA and genomic libraries.
• Confocal immunofluorescence microscopy.
• Protein-protein interaction analysis by Förster resonance energy transfer (FRET).
• Automated determination of metabolites and enzyme activities.
• Protein expression in Escherichia coli, yeast and eukaryotic cell lines. Western blot.
• Two-hybrid system in yeast.

• Dr. MaríaPilar Almajano (Departament d’Enginyeria Química, Escola Tècnica Superior d’Enginyers Industrials de Barcelona, ETSEIB, Universitat Politècnica de Catalunya, UPC): chemical analysis and antioxidant activity in biological samples.

• Dr. John G. Jones and Dr. Ivan Viegas (Center for Neurosciences and Cellular Biology, Universidade de Coimbra, Portugal): Nuclear Magnetic Ressonance  (NMR) to study metabolic flux.

• Dr. Anna Fàbregas (Mimark Diagnostics S.L., Barcelona): design of chitosan-TPP nanoparticles for DNA delivery in vivo.

• Dr. Montserrat Miñarro and Dr. Josep R. Ticó (Departament de Farmàcia i Tecnologia Farmacèutica i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, UB): obtention of chitosan-TPP-DNA nanoparticles.

• Dr. Javier Palazón (Departament de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia i Ciències de l’Alimentació, UB) and Dr. Elisabeth Moyano ( Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, UPF): citotoxicity of vegetal products.

• Dr. Amina Zuberi (Department of Animal Sciences, Quaid-i-Azam University, Islamabad, Pakistan): phylogenetic and nutritional studies in cyprinids.

• Dr. Sedigheh Babaei and Dr. Abedian Kenari (Fisheries Departament, Tarbiat Modares University, Noor, Iran): nutritional studies in gilthead sea bream (Sparus aurata) and Siberian sturgeon (Acipenser baerii).

• Dr. Luis D. S. Murgas (Departamento de Medicina Veterinária, Universidade Federal de Lavras, Brasil): identification of biomarker genes for sex determination in fish.