Search

Your search keyword '"Mato, Jose M"' showing total 316 results
Start Over Author "Mato, Jose M"
316 results on '"Mato, Jose M"'

4. Depletion of mitochondrial methionine adenosyltransferase α1 triggers mitochondrial dysfunction in alcohol-associated liver disease

Author

Barbier-Torres, Lucía, Murray, Ben, Yang, Jin Won, Wang, Jiaohong, Matsuda, Michitaka, Robinson, Aaron, Binek, Aleksandra, Fan, Wei, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Luque-Urbano, Maria, Millet, Oscar, Mavila, Nirmala, Peng, Hui, Ramani, Komal, Gottlieb, Roberta, Sun, Zhaoli, Liangpunsakul, Suthat, Seki, Ekihiro, Van Eyk, Jennifer E, Mato, Jose M, and Lu, Shelly C

Subjects
Biochemistry and Cell Biology, Biological Sciences, Substance Misuse, Liver Disease, Chronic Liver Disease and Cirrhosis, Alcoholism, Alcohol Use and Health, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Good Health and Well Being, Animals, Blotting, Western, Casein Kinase II, Cell Line, Ethanol, Female, Hep G2 Cells, Hepatocytes, Humans, Isoenzymes, Liver, Liver Diseases, Alcoholic, Methionine Adenosyltransferase, Mice, Inbred C57BL, Mitochondria, Mitochondrial Proteins, Mutation, NIMA-Interacting Peptidylprolyl Isomerase, Protein Binding
Abstract

MATα1 catalyzes the synthesis of S-adenosylmethionine, the principal biological methyl donor. Lower MATα1 activity and mitochondrial dysfunction occur in alcohol-associated liver disease. Besides cytosol and nucleus, MATα1 also targets the mitochondria of hepatocytes to regulate their function. Here, we show that mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which phosphorylates MATα1 at Ser114 facilitating interaction with PIN1, thereby inhibiting its mitochondrial localization. Blocking PIN1-MATα1 interaction increased mitochondrial MATα1 levels and protected against alcohol-induced mitochondrial dysfunction and fat accumulation. Normally, MATα1 interacts with mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and fatty acid β-oxidation. Preserving mitochondrial MATα1 content correlates with higher methylation and expression of mitochondrial proteins. Our study demonstrates a role of CK2 and PIN1 in reducing mitochondrial MATα1 content leading to mitochondrial dysfunction in alcohol-associated liver disease.

Published
2022

5. Prospective Metabolomic Studies in Precision Medicine: The AKRIBEA Project

Author

Bizkarguenaga, Maider, Gil-Redondo, Rubén, Bruzzone, Chiara, Bernardo-Seisdedos, Ganeko, Laín, Ana, González-Valle, Beatriz, Embade, Nieves, Mato, José M., Millet, Oscar, Michel, Martin C., Editor-in-Chief, Barrett, James E., Editorial Board Member, Centurión, David, Editorial Board Member, Flockerzi, Veit, Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Meier, Kathryn Elaine, Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Ghini, Veronica, editor, Stringer, Kathleen A., editor, and Luchinat, Claudio, editor

Published
2023
Full Text
View/download PDF

7. Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function

Author

Gonzalez-Rellan, Maria J., Parracho, Tamara, Heras, Violeta, Rodriguez, Amaia, Fondevila, Marcos F., Novoa, Eva, Lima, Natalia, Varela-Rey, Marta, Senra, Ana, Chantada-Vazquez, Maria D.P., Ameneiro, Cristina, Bernardo, Ganeko, Fernandez-Ramos, David, Lopitz-Otsoa, Fernando, Bilbao, Jon, Guallar, Diana, Fidalgo, Miguel, Bravo, Susana, Dieguez, Carlos, Martinez-Chantar, Maria L., Millet, Oscar, Mato, Jose M., Schwaninger, Markus, Prevot, Vincent, Crespo, Javier, Frühbeck, Gema, Iruzubieta, Paula, and Nogueiras, Ruben

Published
2023
Full Text
View/download PDF

8. A global research priority agenda to advance public health responses to fatty liver disease

Author

Lazarus, Jeffrey V., Mark, Henry E., Allen, Alina M., Arab, Juan Pablo, Carrieri, Patrizia, Noureddin, Mazen, Alazawi, William, Alkhouri, Naim, Alqahtani, Saleh A., Arrese, Marco, Bataller, Ramon, Berg, Thomas, Brennan, Paul N., Burra, Patrizia, Castro-Narro, Graciela E., Cortez-Pinto, Helena, Cusi, Kenneth, Dedes, Nikos, Duseja, Ajay, Francque, Sven M., Hagström, Hannes, Huang, Terry T-K., Wajcman, Dana Ivancovsky, Kautz, Achim, Kopka, Christopher J., Krag, Aleksander, Miller, Veronica, Newsome, Philip N., Rinella, Mary E., Romero, Diana, Sarin, Shiv Kumar, Silva, Marcelo, Spearman, C. Wendy, Tsochatzis, Emmanuel A., Valenti, Luca, Villota-Rivas, Marcela, Zelber-Sagi, Shira, Schattenberg, Jörn M., Wong, Vincent Wai-Sun, Younossi, Zobair M., Aberg, Fredrik, Adams, Leon, Al-Naamani, Khalid, Albadawy, Reda M., Alexa, Zinaida, Allison, Michael, Alnaser, Faisal A., Alswat, Khalid, Alvares-da-Silva, Mario Reis, Alvaro, Domenico, Alves-Bezerra, Michele, Andrade, Raul J., Anstee, Quentin M., Awuku, Yaw Asante, Baatarkhuu, Oidov, Baffy, Gyorgy, Bakieva, Shokhista, Bansal, Meena B., Barouki, Robert, Batterham, Rachel L., Behling, Cynthia, Belfort-DeAguiar, Renata, Berzigotti, Annalisa, Betel, Michael, Bianco, Cristiana, Bosi, Emanuele, Boursier, Jerome, Brunt, Elizabeth M., Bugianesi, Elisabetta, Byrne, Christopher J., Cabrera Cabrejos, Maria Cecilia, Caldwell, Stephen, Carr, Rotonya, Castellanos Fernández, Marlen Ivón, Castera, Laurent, Castillo-López, Maria Gabriela, Caussy, Cyrielle, Cerda-Reyes, Eira, Ceriello, Antonio, Chan, Wah- Kheong, Chang, Yoosoo, Charatcharoenwitthaya, Phunchai, Chavez-Tapia, Norberto, Chung, Raymond T., Colombo, Massimo, Coppell, Kirsten, Cotrim, Helma P., Craxi, Antonio, Crespo, Javier, Dassanayake, Anuradha, Davidson, Nicholas O., De Knegt, Robert, de Ledinghen, Victor, Demir, Münevver, Desalegn, Hailemichael, Diago, Moises, Dillon, John F., Dimmig, Bruce, Dirac, M. Ashworth, Dirchwolf, Melisa, Dufour, Jean-François, Dvorak, Karel, Ekstedt, Mattias, El-Kassas, Mohamed, Elsanousi, Osama M., Elsharkawy, Ahmed M., Elwakil, Reda, Eskridge, Wayne, Eslam, Mohammed, Esmat, Gamal, Fan, Jian- Gao, Ferraz, Maria Lucia, Flisiak, Robert, Fortin, Davide, Fouad, Yasser, Freidman, Scott L., Fuchs, Michael, Gadano, Adrian, Gastaldelli, Amalia, Geerts, Anja, Geier, Andreas, George, Jacob, Gerber, Lynn H., Ghazinyan, Hasmik, Gheorghe, Liana, Kile, Denise Giangola, Girala, Marcos, Boon Bee, George Goh, Goossens, Nicolas, Graupera, Isabel, Grønbæk, Henning, Hamid, Saeed, Hebditch, Vanessa, Henry, Zachary, Hickman, Ingrid J., Hobbs, L. Ansley, Hocking, Samantha L., Hofmann, Wolf Peter, Idilman, Ramazan, Iruzubieta, Paula, Isaacs, Scott, Isakov, Vasily A., Ismail, Mona H., Jamal, Mohammad H., Jarvis, Helen, Jepsen, Peter, Jornayvaz, François, Sudhamshu, K.C., Kakizaki, Satoru, Karpen, Saul, Kawaguchi, Takumi, Keating, Shelley E., Khader, Yousef, Kim, Seung Up, Kim, Won, Kleiner, David E., Koek, Ger, Joseph Komas, Narcisse Patrice, Kondili, Loreta A., Koot, Bart G., Korenjak, Marko, Kotsiliti, Eleni, Koulla, Yiannoula, Kugelmas, Carina, Kugelmas, Marcelo, Labidi, Asma, Lange, Naomi F., Lavine, Joel E., Lazo, Mariana, Leite, Nathalie, Lin, Han-Chieh, Lkhagvaa, Undram, Long, Michelle T., Lopez-Jaramillo, Patricio, Lozano, Adelina, Macedo, Maria Paula, Malekzadeh, Reza, Marchesini, Giulio, Marciano, Sebastian, Martinez, Kim, Martínez Vázquez, Sophia E., Mateva, Lyudmila, Mato, José M., Nlombi, Charles Mbendi, McCary, Alexis Gorden, McIntyre, Jeff, McKee, Martin, Mendive, Juan M., Mikolasevic, Ivana, Miller, Pamela S., Milovanovic, Tamara, Milton, Terri, Moreno-Alcantar, Rosalba, Morgan, Timothy R., Motala, Ayesha, Muris, Jean, Musso, Carla, Nava-González, Edna J., Negro, Francesco, Nersesov, Alexander V., Neuschwander-Tetri, Brent A., Nikolova, Dafina, Norris, Suzanne, Novak, Katja, Ocama, Ponsiano, Ong, Janus P., Ong-Go, Arlinking, Onyekwere, Charles, Padilla, Martin, Pais, Raluca, Pan, Calvin, Panduro, Arturo, Panigrahi, Manas K., Papatheodoridis, Georgios, Paruk, Imran, Patel, Keyur, Gonçalves, Carlos Penha, Figueroa, Marlene Pérez, Pérez-Escobar, Juanita, Pericàs, Juan M., Perseghin, Gianluca, Pessoa, Mário Guimarães, Petta, Salvatore, Marques Souza de Oliveira, Claudia Pinto, Prabhakaran, Dorairaj, Pyrsopoulous, Nikolaos, Rabiee, Atoosa, Ramji, Alnoor, Ratziu, Vlad, Ravendhran, Natarajan, Ray, Katrina, Roden, Michael, Romeo, Stefano, Romero-Gómez, Manuel, Rotman, Yaron, Rouabhia, Samir, Rowe, Ian A., Sadirova, Shakhlo, Alkhatry, Maryam Salem, Salupere, Riina, Satapathy, Sanjaya K., Schwimmer, Jeffrey B., Sebastiani, Giada, Seim, Lynn, Seki, Yosuke, Serme, Abdel Karim, Shapiro, David, Sharvadze, Lali, Shaw, Jonathan E., Shawa, Isaac Thom, Shenoy, Thrivikrama, Shibolet, Oren, Shimakawa, Yusuke, Shubrook, Jay H., Singh, Shivaram Prasad, Sinkala, Edford, Skladany, Lubomir, Skrypnyk, Igor, Song, Myeong Jun, Sookoian, Silvia, Sridharan, Kannan, Stefan, Norbert, Stine, Jonathan G., Stratakis, Nikolaos, Sheriff, Dhastagir Sultan, Sundaram, Shikha S., Svegliati-Baroni, Gianluca, Swain, Mark G., Tacke, Frank, Taheri, Shahrad, Tan, Soek-Siam, Tapper, Elliot B., Targher, Giovanni, Tcaciuc, Eugen, Thiele, Maja, Tiniakos, Dina, Tolmane, Ieva, Torre, Aldo, Torres, Esther A., Treeprasertsuk, Sombat, Trenell, Michael, Turcan, Svetlana, Turcanu, Adela, Valantinas, Jonas, van Kleef, Laurens A., Velarde Ruiz Velasco, Jose Antonio, Vesterhus, Mette, Vilar-Gomez, Eduardo, Waked, Imam, Wattacheril, Julia, Wedemeyer, Heiner, Wilkins, Fonda, Willemse, José, Wong, Robert J., Yilmaz, Yusuf, Yki-Järvinen, Hannele, Yu, Ming-Lung, Yumuk, Volkan, Zeybel, Müjdat, Zheng, Kenneth I., Zheng, Ming-Hua, and Huang, Terry T.-K.

Published
2023
Full Text
View/download PDF

9. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Anstee, Quentin M, Daly, Ann K, Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J, Day, Christopher P, Wonders, Kristy, Missier, Paolo, McTeer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M, Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G, Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M, Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K, Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioannis, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J, Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, McGlinchey, Aiden, Mato, Jose M, Millet, Óscar, Dufour, Jean-François, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Rasmussen, Daniel Guldager Kring, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattias, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M P, Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andreas, Trautwein, Christian, Reißing, Johanna, Aithal, Guruprasad P, Francis, Susan, Palaniyappan, Naaventhan, Bradley, Christopher, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W, Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, McLeod, Euan James, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Coxson, Harvey, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Kjær, Mette Skalshøi, Harder, Lea Mørch, Davidsen, Peter, Ellegaard, Jens, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Douglas, Shankar, Sudha, Torstenson, Richard, Lindén, Daniel, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D, Billin, Andrew, Doward, Lynda, Twiss, James, Thakker, Paresh, Derdak, Zoltan, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, Mózes, Ferenc E, Lee, Jenny A, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, van Dijk, Anne-Marieke, Mak, Anne Linde, de Saint Loup, Marc, Shima, Toshihide, Gaia, Silvia, Shalimar, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Lee, Dae Ho, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, and Harrison, Stephen A

Published
2023
Full Text
View/download PDF

10. Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

Author

Simon, Jorge, Nuñez-García, Maitane, Fernández-Tussy, Pablo, Barbier-Torres, Lucía, Fernández-Ramos, David, Gómez-Santos, Beatriz, Buqué, Xabier, Lopitz-Otsoa, Fernando, Goikoetxea-Usandizaga, Naroa, Serrano-Macia, Marina, Rodriguez-Agudo, Rubén, Bizkarguenaga, Maider, Zubiete-Franco, Imanol, Gutiérrez-de Juan, Virginia, Cabrera, Diana, Alonso, Cristina, Iruzubieta, Paula, Romero-Gomez, Manuel, van Liempd, Sebastiaan, Castro, Azucena, Nogueiras, Ruben, Varela-Rey, Marta, Falcón-Pérez, Juan Manuel, Villa, Erica, Crespo, Javier, Lu, Shelly C, Mato, Jose M, Aspichueta, Patricia, Delgado, Teresa C, and Martínez-Chantar, María Luz

Subjects
Biochemistry and Cell Biology, Biological Sciences, Hepatitis, Chronic Liver Disease and Cirrhosis, Liver Disease, Nutrition, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Adult, Animals, Choline, Disease Models, Animal, Female, Glutaminase, Hepatocytes, Humans, Lipid Metabolism, Lipoproteins, VLDL, Liver, Male, Methionine, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease, Oxidative Stress, Phospholipids, Triglycerides, GLS1, GLS2, NAFLD, NASH, TCA cycle, VLDL, folate cycle, glutaminase, methionine cycle, phospholipids, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from the phosphatidylethanolamine N-methyltransferase-mediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.

Published
2020

11. Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency

Author

Robinson, Aaron E., Binek, Aleksandra, Ramani, Komal, Sundararaman, Niveda, Barbier-Torres, Lucía, Murray, Ben, Venkatraman, Vidya, Kreimer, Simion, Ardle, Angela Mc, Noureddin, Mazen, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Gutiérrez de Juan, Virginia, Millet, Oscar, Mato, José M., Lu, Shelly C., and Van Eyk, Jennifer E.

Published
2023
Full Text
View/download PDF

14. PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

Author

Zabala-Letona, Amaia, Arruabarrena-Aristorena, Amaia, Fernandez-Ruiz, Sonia, Viera, Cristina, Carlevaris, Onintza, Ercilla, Amaia, Mendizabal, Isabel, Martin, Teresa, Macchia, Alice, Camacho, Laura, Pujana-Vaquerizo, Mikel, Sanchez-Mosquera, Pilar, Torrano, Verónica, Martin-Martin, Natalia, Zuniga-Garcia, Patricia, Castillo-Martin, Mireia, Ugalde-Olano, Aitziber, Loizaga-Iriarte, Ana, Unda, Miguel, Mato, Jose M., Berra, Edurne, Martinez-Chantar, Maria L., and Carracedo, Arkaitz

Published
2022
Full Text
View/download PDF

16. Molecular dynamics simulation of behaviour of water in nano-confined ionic liquid--water mixtures

Author

Docampo-Álvarez, Borja, Gómez-González, Victor, Montes-Campos, Hadrián, Otero-Mato, José M., Méndez-Morales, Trinidad, Cabeza, Oscar, del Hoyo, Luis J. Luis Gallego, Lynden-Bell, Ruth M., Ivaništšev, Vladislav B., Fedorov, Maxim V., and Varela, Luis M.

Subjects
Condensed Matter - Soft Condensed Matter
Abstract

This work describes the behaviour of water molecules in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid under nanoconfinement between graphene sheets. By means of molecular dynamics simulations, an adsorption of water molecules at the graphene surface is studied. A depletion of water molecules in the vicinity of the neutral and negatively charged graphene surfaces and their adsorption at the positively charged surface are observed in line with the preferential hydration of the ionic liquid anions. The findings are appropriately described using a two-level statistical model. The confinement effect on the structure and dynamics of the mixtures is thoroughly analyzed using the density and the potential of mean force profiles, as well as by the vibrational densities of states of water molecules near the graphene surface. The orientation of water molecules and the water-induced structural transitions in the layer closest to the graphene surface are also discussed., Comment: 14 pages, 7 figures, to appear in Journal of Physics: Condensed Matter

Published
2016
Full Text
View/download PDF

23. SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum

Author

Bruzzone, Chiara, Bizkarguenaga, Maider, Gil-Redondo, Rubén, Diercks, Tammo, Arana, Eunate, García de Vicuña, Aitor, Seco, Marisa, Bosch, Alexandre, Palazón, Asís, San Juan, Itxaso, Laín, Ana, Gil-Martínez, Jon, Bernardo-Seisdedos, Ganeko, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Embade, Nieves, Lu, Shelly, Mato, José M., and Millet, Oscar

Published
2020
Full Text
View/download PDF

25. Deregulated methionine adenosyltransferase α1, c‐Myc, and Maf proteins together promote cholangiocarcinoma growth in mice and humans‡

Author

Yang, Heping, Liu, Ting, Wang, Jiaohong, Li, Tony WH, Fan, Wei, Peng, Hui, Krishnan, Anuradha, Gores, Gregory J, Mato, Jose M, and Lu, Shelly C

Subjects
Digestive Diseases, Genetics, Rare Diseases, Chronic Liver Disease and Cirrhosis, Liver Disease, Liver Cancer, Digestive Diseases - (Gallbladder), Cancer, 1.1 Normal biological development and functioning, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, Oral and gastrointestinal, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Bile Duct Neoplasms, Cholangiocarcinoma, DNA Methylation, E-Box Elements, Gene Expression Regulation, Hep G2 Cells, Humans, MafG Transcription Factor, Male, Methionine Adenosyltransferase, Mice, Inbred C57BL, Proto-Oncogene Proteins c-maf, Repressor Proteins, Salivary alpha-Amylases, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Unlabelledc-Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice, and induction of Maf proteins (MafG and c-Maf) contributes to cholestatic liver injury, whereas S-adenosylmethionine (SAMe) administration is protective. Here, we determined whether there is interplay between c-Myc, Maf proteins, and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in the liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh-28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein-protein interactions, molecular mechanisms, and functional outcomes. We found that c-Myc, MATα1 (encoded by MAT1A), MafG, and c-Maf interact with one another directly. MAT1A expression fell in hepatocytes and bile duct epithelial cells during chronic cholestasis and in murine and human CCA. The opposite occurred with c-Myc, MafG, and c-Maf expression. MATα1 interacts mainly with Mnt in normal liver, but this switches to c-Maf, MafG, and c-Myc in cholestatic livers and CCA. Promoter regions of these genes have E-boxes that are bound by MATα1 and Mnt in normal liver and benign bile duct epithelial cells that switched to c-Myc, c-Maf, and MafG in cholestasis and CCA cells. E-box positively regulates c-Myc, MafG, and c-Maf, but it negatively regulates MAT1A. MATα1 represses, whereas c-Myc, MafG, and c-Maf enhance, E-box-driven promoter activity. Knocking down MAT1A or overexpressing MafG or c-Maf enhanced CCA growth and invasion in vivo.ConclusionThere is a novel interplay between MATα1, c-Myc, and Maf proteins, and their deregulation during chronic cholestasis may facilitate CCA oncogenesis. (Hepatology 2016;64:439-455).

Published
2016

26. Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Author

Murray, Ben, Antonyuk, Svetlana V, Marina, Alberto, Lu, Shelly C, Mato, Jose M, Hasnain, S Samar, and Rojas, Adriana L

Subjects
Cancer, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Catalysis, Catalytic Domain, Crystallography, X-Ray, Humans, Methionine Adenosyltransferase, S-Adenosylmethionine, methionine adenosyltransferase, cell growth, liver cancer, X-ray crystallography, methylation
Abstract

The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligands, providing a "structural movie" of the catalytic steps. High- to atomic-resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE.

Published
2016

27. O-GlcNAcylated p53 in the liver modulates hepatic glucose production

Author

Gonzalez-Rellan, Maria J., Fondevila, Marcos F., Fernandez, Uxia, Rodríguez, Amaia, Varela-Rey, Marta, Veyrat-Durebex, Christelle, Seoane, Samuel, Bernardo, Ganeko, Lopitz-Otsoa, Fernando, Fernández-Ramos, David, Bilbao, Jon, Iglesias, Cristina, Novoa, Eva, Ameneiro, Cristina, Senra, Ana, Beiroa, Daniel, Cuñarro, Juan, DP Chantada-Vazquez, Maria, Garcia-Vence, Maria, Bravo, Susana B., Da Silva Lima, Natalia, Porteiro, Begoña, Carneiro, Carmen, Vidal, Anxo, Tovar, Sulay, Müller, Timo D., Ferno, Johan, Guallar, Diana, Fidalgo, Miguel, Sabio, Guadalupe, Herzig, Stephan, Yang, Won Ho, Cho, Jin Won, Martinez-Chantar, Maria Luz, Perez-Fernandez, Roman, López, Miguel, Dieguez, Carlos, Mato, Jose M., Millet, Oscar, Coppari, Roberto, Woodhoo, Ashwin, Fruhbeck, Gema, and Nogueiras, Ruben

Published
2021
Full Text
View/download PDF

28. Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin‐1

Author

Barbier-Torres, Lucía, Beraza, Naiara, Fernández-Tussy, Pablo, Lopitz-Otsoa, Fernando, Fernández-Ramos, David, Zubiete-Franco, Imanol, Varela-Rey, Marta, Delgado, Teresa C, Gutiérrez, Virginia, Anguita, Juan, Pares, Albert, Banales, Jesús M, Villa, Erica, Caballería, Juan, Alvarez, Luis, Lu, Shelly C, Mato, Jose M, and Martínez-Chantar, María Luz

Subjects
Pediatric, Genetics, Perinatal Period - Conditions Originating in Perinatal Period, Chronic Liver Disease and Cirrhosis, Liver Disease, Rare Diseases, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Animals, Cholestasis, Intrahepatic, Histone Deacetylases, Humans, Liver Diseases, Male, Mice, Prohibitins, Repressor Proteins, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

UnlabelledProhibitin-1 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer, and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease. Expression of PHB1 is markedly reduced in patients with primary biliary cirrhosis and biliary atresia or with Alagille syndrome, two major pediatric cholestatic conditions. In the experimental model of bile duct ligation, silencing of PHB1 induced liver fibrosis, reduced animal survival, and induced bile duct proliferation. Importantly, the modulatory effect of PHB1 is not dependent on its known mitochondrial function. Also, PHB1 interacts with histone deacetylase 4 (HDAC4) in the presence of bile acids. Hence, PHB1 depletion leads to increased nuclear HDAC4 content and its associated epigenetic changes. Remarkably, HDAC4 silencing and the administration of the HDAC inhibitor parthenolide during obstructive cholestasis in vivo promote genomic reprogramming, leading to regression of the fibrotic phenotype in liver-specific Phb1 knockout mice.ConclusionPHB1 is an important mediator of cholestatic liver injury that regulates the activity of HDAC4, which controls specific epigenetic markers; these results identify potential novel strategies to treat liver injury and fibrosis, particularly as a consequence of chronic cholestasis.

Published
2015

29. Methionine Adenosyltransferase 2B–GIT1 Complex Serves as a Scaffold to Regulate Ras/Raf/MEK1/2 Activity in Human Liver and Colon Cancer Cells

Author

Peng, Hui, Li, Tony WH, Yang, Heping, Moyer, Mary P, Mato, Jose M, and Lu, Shelly C

Subjects
Biomedical and Clinical Sciences, Health Sciences, Cancer, Rare Diseases, Liver Disease, Digestive Diseases, Adaptor Proteins, Signal Transducing, Cell Cycle Proteins, Cell Line, Tumor, Colonic Neoplasms, Enzyme Activation, Humans, Liver Neoplasms, Methionine Adenosyltransferase, Mitogen-Activated Protein Kinase Kinases, Protein Binding, Protein Multimerization, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-raf, Up-Regulation, p21-Activated Kinases, ras Proteins, src-Family Kinases, Medical and Health Sciences, Pathology, Biomedical and clinical sciences, Health sciences
Abstract

Methionine adenosyltransferase 2B (MAT2B) encodes for variant proteins V1 and V2 that interact with GIT1 to increase ERK activity and growth in human liver and colon cancer cells. MAT2B or GIT1 overexpression activates MEK. This study explores the mechanism for MEK activation. We examined protein-protein interactions by co-immunoprecipitation and verified by confocal microscopy and pull-down assay using recombinant or in vitro translated proteins. Results were confirmed in an orthotopic liver cancer model. We found that MAT2B and GIT1-mediated MEK1/2 activation was not mediated by PAK1 or Src in HepG2 or RKO cells. Instead, MAT2B and GIT1 interact with B-Raf and c-Raf and enhance recruitment of Raf proteins to MEK1/2. MAT2B-GIT1 activates c-Raf, which is the key mediator for MEK/12 activation, because this still occurred in RKO cells that express constitutively active B-Raf mutant. The mechanism lies with the ability of MAT2B-GIT1 to activate Ras and promote B-Raf/c-Raf heterodimerization. Interestingly, MAT2B but not GIT1 can directly interact with Ras, which increases protein stability. Finally, increased Ras-Raf-MEK signaling occurred in phenotypically more aggressive liver cancers overexpressing MAT2B variants and GIT1. In conclusion, interaction between MAT2B and GIT1 serves as a scaffold and facilitates signaling in multiple steps of the Ras/Raf/MEK/ERK pathway, further emphasizing the importance of MAT2B/GIT1 interaction in cancer growth.

Published
2015

30. miR-873-5p targets mitochondrial GNMT-Complex II interface contributing to non-alcoholic fatty liver disease

Author

Fernández-Tussy, Pablo, Fernández-Ramos, David, Lopitz-Otsoa, Fernando, Simón, Jorge, Barbier-Torres, Lucía, Gomez-Santos, Beatriz, Nuñez-Garcia, Maitane, Azkargorta, Mikel, Gutiérrez-de Juan, Virginia, Serrano-Macia, Marina, Rodríguez-Agudo, Rubén, Iruzubieta, Paula, Anguita, Juan, Castro, Rui E., Champagne, Devin, Rincón, Mercedes, Elortza, Felix, Arslanow, Anita, Krawczyk, Marcin, Lammert, Frank, Kirchmeyer, Mélanie, Behrmann, Iris, Crespo, Javier, Lu, Shelly C., Mato, José M., Varela-Rey, Marta, Aspichueta, Patricia, Delgado, Teresa C., and Martínez-Chantar, María L.

Published
2019
Full Text
View/download PDF

32. Structure and function study of the complex that synthesizes S-adenosylmethionine

Author

Murray, Ben, Antonyuk, Svetlana V, Marina, Alberto, Van Liempd, Sebastiaan M, Lu, Shelly C, Mato, Jose M, Hasnain, S Samar, and Rojas, Adriana L

Subjects
Digestive Diseases, Liver Disease, Complementary and Integrative Health, Liver Cancer, Orphan Drug, Cancer, Rare Diseases, Generic health relevance, methionine adenosyltransferases, cell growth, liver cancer, X-ray scattering, methylation, drug design, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Condensed Matter Physics, Physical Chemistry (incl. Structural)
Abstract

S-Adenosylmethionine (SAMe) is the principal methyl donor of the cell and is synthesized via an ATP-driven process by methionine adenosyltransferase (MAT) enzymes. It is tightly linked with cell proliferation in liver and colon cancer. In humans, there are three genes, mat1A, mat2A and mat2B, which encode MAT enzymes. mat2A and mat2B transcribe MATα2 and MATβ enzyme subunits, respectively, with catalytic and regulatory roles. The MATα2β complex is expressed in nearly all tissues and is thought to be essential in providing the necessary SAMe flux for methylation of DNA and various proteins including histones. In human hepatocellular carcinoma mat2A and mat2B genes are upregulated, highlighting the importance of the MATα2β complex in liver disease. The individual subunits have been structurally characterized but the nature of the complex has remained elusive despite its existence having been postulated for more than 20 years and the observation that MATβ is often co-localized with MATα2. Though SAMe can be produced by MAT(α2)4 alone, this paper shows that the V max of the MATα2β complex is three- to fourfold higher depending on the variants of MATβ that participate in complex formation. Using X-ray crystallography and solution X-ray scattering, the first structures are provided of this 258 kDa functional complex both in crystals and solution with an unexpected stoichiometry of 4α2 and 2βV2 subunits. It is demonstrated that the N-terminal regulates the activity of the complex and it is shown that complex formation takes place surprisingly via the C-terminal of MATβV2 that buries itself in a tunnel created at the interface of the MAT(α2)2. The structural data suggest a unique mechanism of regulation and provide a gateway for structure-based drug design in anticancer therapies.

Published
2014

36. Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function

Author

Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela. Departamento de Fisioloxía, Gonzalez-Rellan, Maria J., Parracho, Tamara, Heras, Violeta, Rodriguez, Amaia, Fondevila, Marcos F., Novoa, Eva, Lima, Natalia, Varela-Rey, Marta, Senra, Ana, Chantada-Vazquez, Maria D.P., Ameneiro, Cristina, Bernardo, Ganeko, Fernandez-Ramos, David, Lopitz-Otsoa, Fernando, Bilbao, Jon, Guallar, Diana, Fidalgo, Miguel, Bravo, Susana, Dieguez, Carlos, Martinez-Chantar, Maria L., Millet, Oscar, Mato, Jose M., Schwaninger, Markus, Prevot, Vincent, Crespo, Javier, Frühbeck, Gema, Iruzubieta, Paula, Nogueiras, Ruben, Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela. Departamento de Fisioloxía, Gonzalez-Rellan, Maria J., Parracho, Tamara, Heras, Violeta, Rodriguez, Amaia, Fondevila, Marcos F., Novoa, Eva, Lima, Natalia, Varela-Rey, Marta, Senra, Ana, Chantada-Vazquez, Maria D.P., Ameneiro, Cristina, Bernardo, Ganeko, Fernandez-Ramos, David, Lopitz-Otsoa, Fernando, Bilbao, Jon, Guallar, Diana, Fidalgo, Miguel, Bravo, Susana, Dieguez, Carlos, Martinez-Chantar, Maria L., Millet, Oscar, Mato, Jose M., Schwaninger, Markus, Prevot, Vincent, Crespo, Javier, Frühbeck, Gema, Iruzubieta, Paula, and Nogueiras, Ruben

Abstract

Objective O-GlcNAcylation is a post-translational modification that directly couples the processes of nutrient sensing, metabolism, and signal transduction, affecting protein function and localization, since the O-linked N-acetylglucosamine moiety comes directly from the metabolism of glucose, lipids, and amino acids. The addition and removal of O-GlcNAc of target proteins are mediated by two highly conserved enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), respectively. Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer, diabetes, and cardiovascular diseases. The contribution of deregulated O-GlcNAcylation to the progression and pathogenesis of NAFLD remains intriguing, and a better understanding of its roles in this pathophysiological context is required to uncover novel avenues for therapeutic intervention. By using a translational approach, our aim is to describe the role of OGT and O-GlcNAcylation in the pathogenesis of NAFLD. Methods We used primary mouse hepatocytes, human hepatic cell lines and in vivo mouse models of steatohepatitis to manipulate O-GlcNAc transferase (OGT). We also studied OGT and O-GlcNAcylation in liver samples from different cohorts of people with NAFLD. Results O-GlcNAcylation was upregulated in the liver of people and animal models with steatohepatitis. Downregulation of OGT in NAFLD-hepatocytes improved diet-induced liver injury in both in vivo and in vitro models. Proteomics studies revealed that mitochondrial proteins were hyper-O-GlcNAcylated in the liver of mice with steatohepatitis. Inhibition of OGT is able to restore mitochondrial oxidation and decrease hepatic lipid content in in vitro and in vivo models of NAFLD. Conclusions These results demonstrate that deregulated hyper-O-GlcNAcylation favors NAFLD progression by reducing mitochondrial oxidation and promoting hepatic lipid accumulation

Published
2023

37. Machine learning algorithm improves the detection of NASH (NAS-based) and at-risk NASH: A development and validation study

Author

Jenny, Lee, Max, Westphal, Yasaman, Vali, Jerome, Boursier, Salvatorre, Petta, Rachel, Ostroff, Leigh, Alexander, Yu, Chen, Celine, Fournier, Andreas, Geier, Sven, Francque, Kristy, Wonder, Dina, Tiniako, Pierre, Bedossa, Mike, Allison, Georgios, Papatheodoridi, Helena, Cortez-Pinto, Raluca, Pai, Jean-Francois, Dufour, Diana Julie, Leeming, Stephen, Harrison, Jeremy, Cobbold, Adriaan G, Holleboom, Hannele, Yki-Järvinen, Javier, Crespo, Mattias, Ekstedt, Guruprasad P, Aithal, Elisabetta, Bugianesi, Manuel, Romero-Gomez, Richard, Torstenson, Morten, Karsdal, Carla, Yuni, Jörn M, Schattenberg, Detlef, Schuppan, Vlad, Ratziu, Clifford, Bra, Kevin, Duffin, Koos, Zwinderman, Michael, Pavlide, Quentin M, Anstee, Patrick M, Bossuyt, Anstee, Quentin M., Daly, Ann K., Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J., Day, Christopher P., Wonders, Kristy, Missier, Paolo, Mcteer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G., Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M., Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K., Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioanni, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J., Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, Mcglinchey, Aiden, Mato, Jose M., Millet, Óscar, Dufour, Jean-Françoi, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Guldager Kring Rasmussen, Daniel, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattia, Kechagias, Stergio, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M. P., Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andrea, Trautwein, Christian, Aithal, Guruprasad P., Francis, Susan, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W., Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, Mcleod, Euan Jame, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Skalshøi Kjær, Mette, Mørch Harder, Lea, Davidsen, Peter, Mikkelsen, Lars Frii, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Dougla, Shankar, Sudha, Torstenson, Richard, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D., Billin, Andrew, Doward, Lynda, Twiss, Jame, Thakker, Paresh, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, Luca, Miele (ORCID:0000-0003-3464-0068), Jenny, Lee, Max, Westphal, Yasaman, Vali, Jerome, Boursier, Salvatorre, Petta, Rachel, Ostroff, Leigh, Alexander, Yu, Chen, Celine, Fournier, Andreas, Geier, Sven, Francque, Kristy, Wonder, Dina, Tiniako, Pierre, Bedossa, Mike, Allison, Georgios, Papatheodoridi, Helena, Cortez-Pinto, Raluca, Pai, Jean-Francois, Dufour, Diana Julie, Leeming, Stephen, Harrison, Jeremy, Cobbold, Adriaan G, Holleboom, Hannele, Yki-Järvinen, Javier, Crespo, Mattias, Ekstedt, Guruprasad P, Aithal, Elisabetta, Bugianesi, Manuel, Romero-Gomez, Richard, Torstenson, Morten, Karsdal, Carla, Yuni, Jörn M, Schattenberg, Detlef, Schuppan, Vlad, Ratziu, Clifford, Bra, Kevin, Duffin, Koos, Zwinderman, Michael, Pavlide, Quentin M, Anstee, Patrick M, Bossuyt, Anstee, Quentin M., Daly, Ann K., Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J., Day, Christopher P., Wonders, Kristy, Missier, Paolo, Mcteer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G., Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M., Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K., Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioanni, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J., Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, Mcglinchey, Aiden, Mato, Jose M., Millet, Óscar, Dufour, Jean-Françoi, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Guldager Kring Rasmussen, Daniel, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattia, Kechagias, Stergio, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M. P., Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andrea, Trautwein, Christian, Aithal, Guruprasad P., Francis, Susan, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W., Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, Mcleod, Euan Jame, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Skalshøi Kjær, Mette, Mørch Harder, Lea, Davidsen, Peter, Mikkelsen, Lars Frii, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Dougla, Shankar, Sudha, Torstenson, Richard, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D., Billin, Andrew, Doward, Lynda, Twiss, Jame, Thakker, Paresh, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, Hytiroglou, Prodromos, and Luca, Miele (ORCID:0000-0003-3464-0068)

Abstract

Background and aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.

Published
2023

39. S-Adenosylmethionine increases circulating very-low density lipoprotein clearance in non-alcoholic fatty liver disease

Author

Martínez-Uña, Maite, Varela-Rey, Marta, Mestre, Daniela, Fernández-Ares, Larraitz, Fresnedo, Olatz, Fernandez-Ramos, David, Juan, Virginia Gutiérrez-de, Martin-Guerrero, Idoia, García-Orad, Africa, Luka, Zigmund, Wagner, Conrad, Lu, Shelly C., García-Monzón, Carmelo, Finnell, Richard H., Aurrekoetxea, Igor, Buqué, Xabier, Martínez-Chantar, M. Luz, Mato, José M., and Aspichueta, Patricia

Published
2015
Full Text
View/download PDF

42. Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis

Author

Fondevila, Marcos F., primary, Fernandez, Uxia, additional, Heras, Violeta, additional, Parracho, Tamara, additional, Gonzalez-Rellan, Maria J., additional, Novoa, Eva, additional, Porteiro, Begoña, additional, Alonso, Cristina, additional, Mayo, Rebeca, additional, da Silva Lima, Natalia, additional, Iglesias, Cristina, additional, Filliol, Aveline A., additional, Senra, Ana, additional, Delgado, Teresa C., additional, Woodhoo, Ashwin, additional, Herrero, Laura, additional, Serra, Dolors, additional, Prevot, Vincent, additional, Schwaninger, Markus, additional, López, Miguel, additional, Dieguez, Carlos, additional, Millet, Oscar, additional, Mato, Jose M., additional, Cubero, Francisco J., additional, Varela-Rey, Marta, additional, Iruzubieta, Paula, additional, Crespo, Javier, additional, Martinez-Chantar, Maria L., additional, Schwabe, Robert F., additional, and Nogueiras, Ruben, additional

Published
2022
Full Text
View/download PDF

44. Hepatoma Cells From Mice Deficient in Glycine N-Methyltransferase Have Increased RAS Signaling and Activation of Liver Kinase B1

Author

Martínez–López, Nuria, García–Rodríguez, Juan L., Varela–Rey, Marta, Gutiérrez, Virginia, Fernández–Ramos, David, Beraza, Naiara, Aransay, Ana M., Schlangen, Karin, Lozano, Juan Jose, Aspichueta, Patricia, Luka, Zigmund, Wagner, Conrad, Evert, Matthias, Calvisi, Diego F., Lu, Shelly C., Mato, José M., and Martínez–Chantar, María L.

Published
2012
Full Text
View/download PDF

46. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Author

Mózes, Ferenc E, Lee, Jenny A, Vali, Yasaman, Alzoubi, Osama, Staufer, Katharina, Trauner, Michael, Paternostro, Rafael, Stauber, Rudolf E, Holleboom, Adriaan G, van Dijk, Anne-Marieke, Mak, Anne Linde, Boursier, Jérôme, de Saint Loup, Marc, Shima, Toshihide, Bugianesi, Elisabetta, Gaia, Silvia, Armandi, Angelo, Shalimar, Lupșor-Platon, Monica, Wong, Vincent Wai-Sun, Li, Guanlin, Wong, Grace Lai-Hung, Cobbold, Jeremy, Karlas, Thomas, Wiegand, Johannes, Sebastiani, Giada, Tsochatzis, Emmanuel, Liguori, Antonio, Yoneda, Masato, Nakajima, Atsushi, Hagström, Hannes, Akbari, Camilla, Hirooka, Masashi, Chan, Wah-Kheong, Mahadeva, Sanjiv, Rajaram, Ruveena, Zheng, Ming-Hua, George, Jacob, Eslam, Mohammed, Petta, Salvatore, Pennisi, Grazia, Viganò, Mauro, Ridolfo, Sofia, Aithal, Guruprasad Padur, Palaniyappan, Naaventhan, Lee, Dae Ho, Ekstedt, Mattias, Nasr, Patrik, Cassinotto, Christophe, de Lédinghen, Victor, Berzigotti, Annalisa, Mendoza, Yuly P, Noureddin, Mazen, Truong, Emily, Fournier-Poizat, Céline, Geier, Andreas, Martic, Miljen, Tuthill, Theresa, Anstee, Quentin M, Harrison, Stephen A, Bossuyt, Patrick M, Pavlides, Michael, Anstee, Quentin M, Daly, Ann K, Govaere, Olivier, Cockell, Simon, Tiniakos, Dina, Bedossa, Pierre, Burt, Alastair, Oakley, Fiona, Cordell, Heather J, Day, Christopher P, Wonders, Kristy, Missier, Paolo, McTeer, Matthew, Vale, Luke, Oluboyede, Yemi, Breckons, Matt, Bossuyt, Patrick M, Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Nieuwdorp, Max, Holleboom, Adriaan G, Verheij, Joanne, Ratziu, Vlad, Clément, Karine, Patino-Navarrete, Rafael, Pais, Raluca, Paradis, Valerie, Schuppan, Detlef, Schattenberg, Jörn M, Surabattula, Rambabu, Myneni, Sudha, Straub, Beate K, Vidal-Puig, Toni, Vacca, Michele, Rodrigues-Cuenca, Sergio, Allison, Mike, Kamzolas, Ioannis, Petsalaki, Evangelia, Campbell, Mark, Lelliott, Chris J, Davies, Susan, Orešič, Matej, Hyötyläinen, Tuulia, McGlinchey, Aiden, Mato, Jose M, Millet, Óscar, Dufour, Jean-François, Berzigotti, Annalisa, Masoodi, Mojgan, Pavlides, Michael, Harrison, Stephen, Neubauer, Stefan, Cobbold, Jeremy, Mozes, Ferenc, Akhtar, Salma, Olodo-Atitebi, Seliat, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Andersson, Anneli, Wigley, Ioan, Romero-Gómez, Manuel, Gómez-González, Emilio, Ampuero, Javier, Castell, Javier, Gallego-Durán, Rocío, Fernández, Isabel, Montero-Vallejo, Rocío, Karsdal, Morten, Rasmussen, Daniel Guldager Kring, Leeming, Diana Julie, Sinisi, Antonia, Musa, Kishwar, Sandt, Estelle, Tonini, Manuela, Bugianesi, Elisabetta, Rosso, Chiara, Armandi, Angelo, Marra, Fabio, Gastaldelli, Amalia, Svegliati, Gianluca, Boursier, Jérôme, Francque, Sven, Vonghia, Luisa, Driessen, Ann, Ekstedt, Mattias, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, Arola, Johanna, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Rodrigues, Cecilia M P, Valenti, Luca, Pelusi, Serena, Petta, Salvatore, Pennisi, Grazia, Miele, Luca, Geier, Andreas, Trautwein, Christian, Reißing, Johanna, Aithal, Guruprasad P, Francis, Susan, Palaniyappan, Naaventhan, Bradley, Christopher, Hockings, Paul, Schneider, Moritz, Newsome, Philip, Hübscher, Stefan, Wenn, David, Rosenquist, Christian, Trylesinski, Aldo, Mayo, Rebeca, Alonso, Cristina, Duffin, Kevin, Perfield, James W, Chen, Yu, Yunis, Carla, Tuthill, Theresa, Harrington, Magdalena Alicia, Miller, Melissa, Chen, Yan, McLeod, Euan James, Ross, Trenton, Bernardo, Barbara, Schölch, Corinna, Ertle, Judith, Younes, Ramy, Oldenburger, Anouk, Coxson, Harvey, Ostroff, Rachel, Alexander, Leigh, Biegel, Hannah, Kjær, Mette Skalshøi, Harder, Lea Mørch, Davidsen, Peter, Ellegaard, Jens, Balp, Maria-Magdalena, Brass, Clifford, Jennings, Lori, Martic, Miljen, Löffler, Jürgen, Applegate, Douglas, Shankar, Sudha, Torstenson, Richard, Lindén, Daniel, Fournier-Poizat, Céline, Llorca, Anne, Kalutkiewicz, Michael, Pepin, Kay, Ehman, Richard, Horan, Gerald, Ho, Gideon, Tai, Dean, Chng, Elaine, Patterson, Scott D, Billin, Andrew, Doward, Lynda, Twiss, James, Thakker, Paresh, Derdak, Zoltan, Landgren, Henrik, Lackner, Carolin, Gouw, Annette, and Hytiroglou, Prodromos

Abstract

Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

Published
2023
Full Text
View/download PDF

49. HuR/Methyl-HuR and AUF1 Regulate the MAT Expressed During Liver Proliferation, Differentiation, and Carcinogenesis

Author

Vázquez–Chantada, Mercedes, Fernández–Ramos, David, Embade, Nieves, Martínez–Lopez, Nuria, Varela–Rey, Marta, Woodhoo, Ashwin, Luka, Zigmund, Wagner, Conrad, Anglim, Paul P., Finnell, Richard H., Caballería, Juan, Laird–Offringa, Ite A., Gorospe, Myriam, Lu, Shelly C., Mato, José M., and Martínez–Chantar, M. Luz

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results