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2. Methods to Study Metabolomics

Author

Fenizia, Simona, Scoditti, Egeria, Gastaldelli, Amalia, Lenzi, Andrea, Series Editor, Jannini, Emmanuele A., Series Editor, Federici, Massimo, editor, and Menghini, Rossella, editor

Published
2024
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3. Brain histone beta-hydroxybutyrylation couples metabolism with gene expression

Author

Cornuti, Sara, Chen, Siwei, Lupori, Leonardo, Finamore, Francesco, Carli, Fabrizia, Samad, Muntaha, Fenizia, Simona, Caldarelli, Matteo, Damiani, Francesca, Raimondi, Francesco, Mazziotti, Raffaele, Magnan, Christophe, Rocchiccioli, Silvia, Gastaldelli, Amalia, Baldi, Pierre, and Tognini, Paola

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Genetics, Biological Sciences, Brain Disorders, Human Genome, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Mice, Animals, Histones, 3-Hydroxybutyric Acid, Ketone Bodies, Brain, Gene Expression, Fasting, Cerebral cortex, Beta-hydroxybutyrylation, Transcriptome, Epigenome, Physiology, Clinical Sciences, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics, Oncology and carcinogenesis
Abstract

Little is known about the impact of metabolic stimuli on brain tissue at a molecular level. The ketone body beta-hydroxybutyrate (BHB) can be a signaling molecule regulating gene transcription. Thus, we assessed lysine beta-hydroxybutyrylation (K-bhb) levels in proteins extracted from the cerebral cortex of mice undergoing a ketogenic metabolic challenge (48 h fasting). We found that fasting enhanced K-bhb in a variety of proteins including histone H3. ChIP-seq experiments showed that K9 beta-hydroxybutyrylation of H3 (H3K9-bhb) was significantly enriched by fasting on more than 8000 DNA loci. Transcriptomic analysis showed that H3K9-bhb on enhancers and promoters correlated with active gene expression. One of the most enriched functional annotations both at the epigenetic and transcriptional level was "circadian rhythms''. Indeed, we found that the diurnal oscillation of specific transcripts was modulated by fasting at distinct zeitgeber times both in the cortex and suprachiasmatic nucleus. Moreover, specific changes in locomotor activity daily features were observed during re-feeding after 48-h fasting. Thus, our results suggest that fasting remarkably impinges on the cerebral cortex transcriptional and epigenetic landscape, and BHB acts as a powerful epigenetic molecule in the brain through direct and specific histone marks remodeling in neural tissue cells.

Published
2023

10. Altered fatty acid metabolism rewires cholangiocarcinoma stemness features

Author

Lori, Giulia, Pastore, Mirella, Navari, Nadia, Piombanti, Benedetta, Booijink, Richell, Rovida, Elisabetta, Tusa, Ignazia, Lewinska, Monika, Andersen, Jesper B., Lottini, Tiziano, Arcangeli, Annarosa, Taddei, Maria Letizia, Pranzini, Erica, Mancini, Caterina, Anceschi, Cecilia, Madiai, Stefania, Sacco, Elena, Rota, Stefano, Trapani, Adriana, Agrimi, Gennaro, Ramazzotti, Matteo, Ostano, Paola, Peraldo Neia, Caterina, Parri, Matteo, Carli, Fabrizia, Sabatini, Silvia, Gastaldelli, Amalia, Marra, Fabio, and Raggi, Chiara

Published
2024
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11. 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
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12. 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
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14. Obesity-Related Insulin Resistance: The Central Role of Adipose Tissue Dysfunction

Author

Mocciaro, Gabriele, Gastaldelli, Amalia, Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Eckel, Juergen, editor, and Clément, Karine, editor

Published
2022
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15. WED-263 A machine learning approach to identify patient features associated with metabolic dysfunction-associated steatohepatitis from the United Kingdom biobank

Author

Schattenberg, Jörn M, primary, Gastaldelli, Amalia, additional, Malhi, Harmeet, additional, Allen, Alina M, additional, Noureddin, Mazen, additional, Karamchandani, Umesh, additional, Romero, Jonathon, additional, Henstock, Peter, additional, Emir, Birol, additional, and Sanyal, Arun J, additional

Published
2024
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17. Prevalence and predictors of non-alcoholic steatohepatitis in subjects with morbid obesity and with or without type 2 diabetes

Author

Lembo, Erminia, Russo, Maria Francesca, Verrastro, Ornella, Anello, Danila, Angelini, Giulia, Iaconelli, Amerigo, Guidone, Caterina, Stefanizzi, Gianluigi, Ciccoritti, Luigi, Greco, Francesco, Sessa, Luca, Riccardi, Laura, Pompili, Maurizio, Raffaelli, Marco, Vecchio, Fabio Maria, Bornstein, Stefan R., Mingrone, Geltrude, Gastaldelli, Amalia, and Capristo, Esmeralda

Published
2022
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23. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Author

Clark, James, Cordell, Heather J., Darlay, Rebecca, Day, Christopher P., Hardy, Tim, Liu, Yang-Lin, Oakley, Fiona, Palmer, Jeremy, Queen, Rachel, Wonders, Kristy, Bossuyt, Patrick M., Holleboom, Adriaan G., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Clement, Karine, Pais, Raluca, Schuppan, Detlef, Allison, Michael, Cuenca, Sergio Rodriguez, Pellegrinelli, Vanessa, Vacca, Michele, Vidal-Puig, Antonio, Hyötyläinen, Tuulia, McGlinchey, Aidan, Orešič, Matej, Sen, Partho, Mato, Jose, Millet, Óscar, Dufour, Jean-Francois, Harrison, Stephen, Neubauer, Stefan, Pavlides, Michael, Mozes, Ferenc, Akhtar, Salma, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Erpicum, Charlotte, Romero-Gomez, Manuel, Gallego-Durán, Rocío, Fernández, Isabel, Karsdal, Morten, Leeming, Diana, Fisker, Mette Juul, Erhardtsen, Elisabeth, Rasmussen, Daniel, Qvist, Per, Sinisi, Antonia, Sandt, Estelle, Tonini, Maria Manuela, Parola, Maurizio, Rosso, Chiara, Marra, Fabio, Gastaldelli, Amalia, Francque, Sven, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Valenti, Luca, Petta, Salvatore, Miele, Luca, Geier, Andreas, Trautwein, Christian, Hockings, Paul, Newsome, Phil, Wenn, David, Pereira Rodrigues, Cecília Maria, Hanf, Rémy, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, Yunis, Carla, Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Kjær, Mette Skalshøi, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Fournier, Céline, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, Twiss, James, Johnson, Katherine, Leary, Peter J., Govaere, Olivier, Barter, Matthew J., Charlton, Sarah H., Cockell, Simon J., Tiniakos, Dina, Zatorska, Michalina, Bedossa, Pierre, Brosnan, M. Julia, Cobbold, Jeremy F., Ekstedt, Mattias, Aithal, Guruprasad P., Clément, Karine, Schattenberg, Jörn M., Boursier, Jerome, Ratziu, Vlad, Bugianesi, Elisabetta, Anstee, Quentin M., and Daly, Ann K.

Published
2022
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24. GLP-1 Receptor Agonist Treatment Improves Fasting and Postprandial Lipidomic Profiles Independently of Diabetes and Weight Loss.

Author

Della Pepa, Giuseppe, Patrício, Bárbara G., Carli, Fabrizia, Sabatini, Silvia, Astiarraga, Brenno, Ferrannini, Ele, Camastra, Stefania, and Gastaldelli, Amalia

Subjects
GLUCAGON-like peptide 1, SATURATED fatty acids, TIME-of-flight mass spectrometry, FREE fatty acids, GAS chromatography/Mass spectrometry (GC-MS)
Abstract

Treatment with glucagon-like peptide 1 receptor agonists reduces liver steatosis and cardiometabolic risk (CMR). Few data are available on lipid metabolism, and no information is available on the postprandial lipidomic profile. Thus, we investigated how exenatide treatment changes lipid metabolism and composition during fasting and after a mixed-meal tolerance test (MMTT) in adults with severe obesity without diabetes. Thirty individuals (26 females and 4 males, 30–60 years old, BMI >40 kg/m2, HbA1c 5.76%) were assigned (1:1) to diet with exenatide 10 μg twice daily treatment (n = 15) or without treatment as control (n = 15) for 3 months. Fasting and postprandial lipidomic profile (by liquid chromatography quadrupole time-of-flight mass spectrometry) and fatty acid metabolism (following a 6-h MMTT/tracer study) and composition (by gas chromatography-mass spectrometry) were evaluated before and after treatment. Both groups had slight weight loss (−5.5% vs. −1.9%, exenatide vs. control; P = 0.052). During fasting, exenatide, compared with control, reduced some ceramides (CERs) and lysophosphatidylcholines (LPCs) previously associated with CMR, while relatively increasing unsaturated phospholipid species (phosphatidylcholine [PC], LPC) with protective effects on CMR, although concentrations of total lipid species were unchanged. During MMTT, both groups showed suppressed lipolysis equal to baseline, but exenatide significantly lowered free fatty acid clearance and postprandial triacyclglycerol (TAG) concentrations, particularly saturated TAGs with 44–54 carbons. Exenatide also reduced some postprandial CERs, PCs, and LPCs previously linked to CMR. These changes in lipidomic profile remained statistically significant after adjusting for weight loss. Exenatide improved fasting and postprandial lipidomic profiles associated with CMR mainly by reducing saturated postprandial TAGs and CERs independently of weight loss and diabetes. Article Highlights: Few data are available on the effect of glucagon-like peptide 1 receptor agonists on lipid metabolism, and no information is available on the postprandial lipidomic profile. In adults without diabetes but with severe obesity, 3-month treatment with exenatide improved fasting and postprandial lipidomic profiles associated with cardiometabolic risk by decreasing saturated species (triacylglycerols [TAGs], ceramides, lysophosphatidylcholines) while increasing seven unsaturated phospholipid species (phosphatidylcholine, lysophosphatidylcholine) with protective effects on cardiometabolic risk compared with control. Exenatide blunted the rise in postprandial triglycerides, especially saturated TAGs. Postprandial triglyceride reduction was associated to decreased postprandial free fatty acid clearance, with lower saturated free fatty acid incorporation into newly synthesized lipids (TAGs and ceramides). [ABSTRACT FROM AUTHOR]

Published
2024
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26. TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models

Author

Longo, Miriam, Meroni, Marica, Paolini, Erika, Erconi, Veronica, Carli, Fabrizia, Fortunato, Francesco, Ronchi, Dario, Piciotti, Roberto, Sabatini, Silvia, Macchi, Chiara, Alisi, Anna, Miele, Luca, Soardo, Giorgio, Comi, Giacomo Pietro, Valenti, Luca, Ruscica, Massimiliano, Fracanzani, Anna L., Gastaldelli, Amalia, and Dongiovanni, Paola

Published
2022
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28. Disparity-filtered differential correlation network analysis: a case study on CRC metabolomics

Author

Sabatini Silvia and Gastaldelli Amalia

Subjects
colorectal cancer (crc), differential network analysis, disparity filter, metabolomics, Biotechnology, TP248.13-248.65
Abstract

Differential network analysis has become a widely used technique to investigate changes of interactions among different conditions. Although the relationship between observed interactions and biochemical mechanisms is hard to establish, differential network analysis can provide useful insights about dysregulated pathways and candidate biomarkers. The available methods to detect differential interactions are heterogeneous and often rely on assumptions that are unrealistic in many applications. To address these issues, we develop a novel method for differential network analysis, using the so-called disparity filter as network reduction technique. In addition, we propose a classification model based on the inferred network interactions. The main novelty of this work lies in its ability to preserve connections that are statistically significant with respect to a null model without favouring any resolution scale, as a hard threshold would do, and without Gaussian assumptions. The method was tested using a published metabolomic dataset on colorectal cancer (CRC). Detected hub metabolites were consistent with recent literature and the classifier was able to distinguish CRC from polyp and healthy subjects with great accuracy. In conclusion, the proposed method provides a new simple and effective framework for the identification of differential interaction patterns and improves the biological interpretation of metabolomics data.

Published
2021
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30. Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control

Author

Della Pepa, Giuseppe, primary, Carli, Fabrizia, additional, Sabatini, Silvia, additional, Pezzica, Samantha, additional, Russo, Marco, additional, Vitale, Marilena, additional, Masulli, Maria, additional, Riccardi, Gabriele, additional, Rivellese, Angela A., additional, Vaccaro, Olga, additional, Bozzetto, Lutgarda, additional, and Gastaldelli, Amalia, additional

Published
2024
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34. Healthy aging: the INTECMAN project

Author

Laurino, Marco, Alfì, Gaspare, Billeci, Lucia, Bortone, Ilaria, Buzzigoli, Emma, Cecchi, Antonella, Del Ry, Silvia, Gastaldelli, Amalia, Lai, Elisa, Morales, Maria Aurora, Pagni, Cristina, Passino, Claudio, Severino, Silvia, Tonacci, Alessandro, Gemignani, Angelo, and Trivella, Maria Giovanna

Published
2021
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36. A global action agenda for turning the tide on fatty liver disease

Author

Lazarus, J, Mark, H, Allen, A, Arab, J, Carrieri, P, Noureddin, M, Alazawi, W, Alkhouri, N, Alqahtani, S, Anstee, Q, Arrese, M, Bataller, R, Berg, T, Brennan, P, Burra, P, Castro-Narro, G, Cortez-Pinto, H, Cusi, K, Dedes, N, Duseja, A, Francque, S, Gastaldelli, A, Hagström, H, Huang, T, Ivancovsky Wajcman, D, Kautz, A, Kopka, C, Krag, A, Newsome, P, Rinella, M, Romero, D, Sarin, S, Silva, M, Spearman, C, Terrault, N, Tsochatzis, E, Valenti, L, Villota-Rivas, M, Zelber-Sagi, S, Schattenberg, J, Wong, V, Younossi, Z, Perseghin, G, Lazarus, Jeffrey V, Mark, Henry E, Allen, Alina M, Arab, Juan Pablo, Carrieri, Patrizia, Noureddin, Mazen, Alazawi, William, Alkhouri, Naim, Alqahtani, Saleh A, Anstee, Quentin M, 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, Gastaldelli, Amalia, Hagström, Hannes, Huang, Terry T K, Ivancovsky Wajcman, Dana, Kautz, Achim, Kopka, Christopher J, Krag, Aleksander, Newsome, Philip N, Rinella, Mary E, Romero, Diana, Sarin, Shiv Kumar, Silva, Marcelo, Spearman, C Wendy, Terrault, Norah A, Tsochatzis, Emmanuel A, Valenti, Luca, Villota-Rivas, Marcela, Zelber-Sagi, Shira, Schattenberg, Jörn M, Wong, Vincent Wai-Sun, Younossi, Zobair M, Perseghin, Gianluca, Lazarus, J, Mark, H, Allen, A, Arab, J, Carrieri, P, Noureddin, M, Alazawi, W, Alkhouri, N, Alqahtani, S, Anstee, Q, Arrese, M, Bataller, R, Berg, T, Brennan, P, Burra, P, Castro-Narro, G, Cortez-Pinto, H, Cusi, K, Dedes, N, Duseja, A, Francque, S, Gastaldelli, A, Hagström, H, Huang, T, Ivancovsky Wajcman, D, Kautz, A, Kopka, C, Krag, A, Newsome, P, Rinella, M, Romero, D, Sarin, S, Silva, M, Spearman, C, Terrault, N, Tsochatzis, E, Valenti, L, Villota-Rivas, M, Zelber-Sagi, S, Schattenberg, J, Wong, V, Younossi, Z, Perseghin, G, Lazarus, Jeffrey V, Mark, Henry E, Allen, Alina M, Arab, Juan Pablo, Carrieri, Patrizia, Noureddin, Mazen, Alazawi, William, Alkhouri, Naim, Alqahtani, Saleh A, Anstee, Quentin M, 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, Gastaldelli, Amalia, Hagström, Hannes, Huang, Terry T K, Ivancovsky Wajcman, Dana, Kautz, Achim, Kopka, Christopher J, Krag, Aleksander, Newsome, Philip N, Rinella, Mary E, Romero, Diana, Sarin, Shiv Kumar, Silva, Marcelo, Spearman, C Wendy, Terrault, Norah A, Tsochatzis, Emmanuel A, Valenti, Luca, Villota-Rivas, Marcela, Zelber-Sagi, Shira, Schattenberg, Jörn M, Wong, Vincent Wai-Sun, Younossi, Zobair M, and Perseghin, Gianluca

Abstract

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce fatty liver disease prevalence and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

Published
2024

37. ForePass endoscopic bypass device for obesity and insulin resistance-metabolic treatment in a swine model

Author

Angelini, Giulia; https://orcid.org/0000-0001-6753-745X, Galvao Neto, Manoel; https://orcid.org/0000-0003-4549-3606, Boskoski, Ivo; https://orcid.org/0000-0001-8194-2670, Caristo, Maria Emiliana, Russo, Sara, Proto, Luca, Previti, Elena, Olsson, Lisa; https://orcid.org/0000-0001-9730-1915, Aggarwal, Hobby, Pezzica, Samantha, Ferrari, Elisa, Bove, Vincenzo, Genco, Alfredo, Bornstein, Stefan; https://orcid.org/0000-0002-5211-2536, Tremaroli, Valentina, Gastaldelli, Amalia; https://orcid.org/0000-0003-2594-1651, Mingrone, Geltrude; https://orcid.org/0000-0003-2021-528X, Angelini, Giulia; https://orcid.org/0000-0001-6753-745X, Galvao Neto, Manoel; https://orcid.org/0000-0003-4549-3606, Boskoski, Ivo; https://orcid.org/0000-0001-8194-2670, Caristo, Maria Emiliana, Russo, Sara, Proto, Luca, Previti, Elena, Olsson, Lisa; https://orcid.org/0000-0001-9730-1915, Aggarwal, Hobby, Pezzica, Samantha, Ferrari, Elisa, Bove, Vincenzo, Genco, Alfredo, Bornstein, Stefan; https://orcid.org/0000-0002-5211-2536, Tremaroli, Valentina, Gastaldelli, Amalia; https://orcid.org/0000-0003-2594-1651, and Mingrone, Geltrude; https://orcid.org/0000-0003-2021-528X

Published
2024

39. The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice.

Author

Reis-Costa, Ana, Belew, Getachew D., Viegas, Ivan, Tavares, Ludgero C., Meneses, Maria João, Patrício, Bárbara, Gastaldelli, Amalia, Macedo, Maria Paula, and Jones, John G.

Abstract

Background: In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood. Methods: Using deuterated water, we measured DNL in mice fed 18-weeks with standard chow (SC), SC supplemented with 55/45-fructose/glucose in the drinking water at 30% (w/v) (HS), high-fat chow (HF), and HF with HS supplementation (HFHS). Liver glycogen levels and its sources were also measured. For HS and HFHS mice, pentose phosphate (PP) fluxes and fructose contributions to DNL and glycogen were measured using [U-13C]fructose. Results: The lipogenic diets caused significantly higher liver triglyceride levels compared to SC. DNL rates were suppressed in HF compared to SC and were partially restored in HFHS but supplied a minority of the additional triglyceride in HFHS compared to HF. Fructose contributed a significantly greater fraction of newly synthesized saturated fatty acids compared to oleic acid in both HS and HFHS. Glycogen levels were not different between diets, but significant differences in Direct and Indirect pathway contributions to glycogen synthesis were found. PP fluxes were similar in HS and HFHS mice and were insufficient to account for DNL reducing equivalents. Conclusions: Despite amplifying the lipogenic effects of fat, the fact that sugar-activated DNL per se barely contributes suggests that its role is likely more relevant in the inhibition of fatty acid oxidation. Fructose promotes lipogenesis of saturated over unsaturated fatty acids and contributes to maintenance of glycogen levels. PP fluxes associated with sugar conversion to fat account for a minor fraction of DNL reducing equivalents. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Urinary Bisphenol A and Bis(2-Ethylhexyl) Phthalate Metabolite Concentrations in Children with Obesity: A Case-Control Study.

Author

Deodati, Annalisa, Bottaro, Giorgia, Germani, Daniela, Carli, Fabrizia, Tait, Sabrina, Busani, Luca, Della Latta, Veronica, Pala, Anna Paola, Maranghi, Francesca, Tassinari, Roberta, Gastaldelli, Amalia, La Rocca, Cinzia, and Cianfarani, Stefano

Subjects
OVERWEIGHT children, HIGH performance liquid chromatography, CHILDHOOD obesity, BISPHENOL A, MEDIAN (Mathematics), PHTHALATE esters
Abstract

Introduction: Obesity is a worldwide public health problem. Experimental animal and in vitro studies suggest that the exposure to BPA and phthalates are associated to a higher risk of obesity. Objective: The objective of the study was to determine urinary excretion of bisphenol A and phthalates in obese and normal weight children. Methods: A case-control study was conducted in 122 children. Sixty-six obese children, 36 girls (mean age 8.41 ± 1.27 years), and 30 boys (mean age 8.51 ± 1.33 years) and 56 normal weight children, 27 girls (mean age 7.64 ± 1.49 years), and 29 boys (mean age 7.77 ± 1.56 years) were studied. Urinary BPA and bis(2-ethylhexyl) phthalate (DEHP) metabolites (MEHP, MEHHP, and MEOHP) were measured, respectively, by gas chromatography and high-performance liquid chromatography. Individual determinants of exposure were evaluated through "ad hoc" questionnaires. Results: BPA and DEHP metabolites were detectable in obese and normal weight children. Obese girls showed significantly higher BPA concentrations in comparison with normal weight girls (means 10.77, 95% CI = 7.02–16.53 vs. 5.50, 95% CI = 3.93–7.71 μg/g creatinine, respectively, p < 0.02). The first step of DEHP metabolic rate was significantly higher in obese girls compared with controls (p < 0.05). DEHP metabolites correlated significantly with leptin concentrations in obese girls (p < 0.03). A higher risk of obesity was found in children with BPA levels above the median values with the habit to eat food packaged (OR = 11.09, 95% CI = 1.28–95.78). Conclusions: These findings show that a higher exposure to BPA is associated with the risk of obesity in girls. Further studies are needed to unveil the cause-effect relationship. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Vagal activation alters prandial bile acid composition and glycemia in patients with hypoglycemia after Roux‐en‐Y gastric bypass surgery.

Author

Honka, Henri, Bhattacharjee, Jashdeep, Zadeh, Mansour, Kohli, Rohit, Gastaldelli, Amalia, and Salehi, Marzieh

Subjects
GASTRIC bypass, BILE acids, GLUCAGON-like peptide 1, HYPOGLYCEMIA, BLOOD sugar, DEOXYCHOLIC acid
Abstract

Background: Altered prandial glycemic response after Roux‐en‐Y gastric bypass (RYGB) is exaggerated in patients with post‐RYGB hypoglycemia. Increased contribution of glucagon‐like peptide 1 (GLP‐1) to prandial insulin secretion plays a key role in developing hypoglycemia after RYGB, but the role of nonhormonal gut factors remains unknown. Here, the effect of vagal activation on prandial bile acid (BA) composition in relation to glucose, insulin and gut hormone responses was examined in a small size group of nondiabetic subjects after RYGB with intact gallbladder compared to nonoperated controls. Methods: Concentrations of blood glucose, hormones, and BAs were measured in two RYGB subjects with documented hypoglycemia (HGB), three asymptomatic RYGB‐treated subjects (AGB), and four nonoperated controls with intact gallbladders during a meal‐tolerance test with (MTT‐Sham) and without (MTT) preceding modified sham feeding (chew and spit). Key Results: Meal ingestion raised serum total BAs in RYGB‐treated subjects without any effect in nonoperated controls. Modified sham feeding similarly increased meal‐induced responses of conjugated BAs (CBAs) in all subjects (p < 0.05 compared to MTT alone), whereas unconjugated BAs (UBAs), mainly deoxycholic and chenodeoxycholic acid, were raised only in the HGB group (p < 0.001 for interaction). Prandial UBAs had an inverse correlation with glucose nadir (r = −0.75, p < 0.05) and were directly associated with ISR and GLP‐1 during MTT‐Sham. Conclusions & Inferences: In this small cohort, vagal activation by modified sham feeding increases prandial CBAs in both operated and nonoperated subjects but enhances UBAs only in patients with documented post‐RYGB hypoglycemia. Our findings highlight a potential role for nonhormonal gut factors, such as BA and gut microbiome, in glucose abnormalities after RYGB. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Is there an association between commonly employed biomarkers of liver fibrosis and liver stiffness in the general population?

Author

Foschi, Francesco Giuseppe, Domenicali, Marco, Giacomoni, Pierluigi, Dall’Aglio, Anna Chiara, Conti, Fabio, Borghi, Alberto, Bevilacqua, Vittoria, Napoli, Lucia, Mirici, Federica, Cucchetti, Alessandro, Ercolani, Giorgio, Gardini, Andrea Casadei, Bellentani, Stefano, Gastaldelli, Amalia, Giuffrè, Mauro, Tiribelli, Claudio, and Bedogni, Giorgio

Published
2020
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44. Pathogenesis

Author

Walker, Mark, additional, Yu, Xuefei, additional, and Gastaldelli, Amalia, additional

Published
2021
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45. ForePass endoscopic bypass device for obesity and insulin resistance—metabolic treatment in a swine model

Author

Angelini, Giulia, primary, Galvao Neto, Manoel, additional, Boskoski, Ivo, additional, Caristo, Maria Emiliana, additional, Russo, Sara, additional, Proto, Luca, additional, Previti, Elena, additional, Olsson, Lisa, additional, Aggarwal, Hobby, additional, Pezzica, Samantha, additional, Ferrari, Elisa, additional, Bove, Vincenzo, additional, Genco, Alfredo, additional, Bornstein, Stefan, additional, Tremaroli, Valentina, additional, Gastaldelli, Amalia, additional, and Mingrone, Geltrude, additional

Published
2023
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50. The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

Author

Jensen, Charlotte Harken, Kosmina, Rok, Rydén, Mikael, Baun, Christina, Hvidsten, Svend, Andersen, Marianne Skovsager, Christensen, Louise Lehmann, Gastaldelli, Amalia, Marraccini, Paolo, Arner, Peter, Jørgensen, Christian Damsgaard, Laborda, Jorge, Holst, Jens Juul, and Andersen, Ditte Caroline

Published
2019
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