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3. Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis

Author

Cabré, Noemí, Luciano-Mateo, Fedra, Chapski, Douglas J, Baiges-Gaya, Gerard, Fernández-Arroyo, Salvador, Hernández-Aguilera, Anna, Castañé, Helena, Rodríguez-Tomàs, Elisabet, París, Marta, Sabench, Fàtima, Del Castillo, Daniel, del Bas, Josep M, Tomé, Mercedes, Bodineau, Clément, Sola-García, Alejandro, López-Miranda, José, Martín-Montalvo, Alejandro, Durán, Raúl V, Vondriska, Thomas M, Rosa-Garrido, Manuel, Camps, Jordi, Menéndez, Javier A, and Joven, Jorge

Subjects
Biochemistry and Cell Biology, Biological Sciences, Obesity, Clinical Research, Liver Disease, Chronic Liver Disease and Cirrhosis, Human Genome, Digestive Diseases, Biotechnology, Genetics, Hepatitis, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Gastrectomy, Humans, Ketoglutaric Acids, Laparoscopy, Non-alcoholic Fatty Liver Disease, Obesity, Morbid, TOR Serine-Threonine Kinases, bariatric surgery, DNA methylation, energy metabolism, epigenetics, functional studies, glutaminolysis, multi-omics approach, Other Chemical Sciences, Other Biological Sciences, Chemical Physics, Biochemistry and cell biology, Microbiology, Medicinal and biomolecular chemistry
Abstract

The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.

Published
2022

5. Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss

Author

Jiménez-Franco, Andrea, Castañé, Helena, Martínez-Navidad, Cristian, Placed-Gallego, Cristina, Hernández-Aguilera, Anna, Fernández-Arroyo, Salvador, Samarra, Iris, Canela-Capdevila, Marta, Arenas, Meritxell, Zorzano, Antonio, Hernández-Alvarez, María Isabel, Castillo, Daniel del, Paris, Marta, Menendez, Javier A., Camps, Jordi, and Joven, Jorge

Published
2024
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7. Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD

Author

Marsal-Beltran, Anna, Rodríguez-Castellano, Adrià, Astiarraga, Brenno, Calvo, Enrique, Rada, Patricia, Madeira, Ana, Rodríguez-Peña, M-Mar, Llauradó, Gemma, Núñez-Roa, Catalina, Gómez-Santos, Beatriz, Maymó-Masip, Elsa, Bosch, Ramon, Frutos, María Dolores, Moreno-Navarrete, José María, Ramos-Molina, Bruno, Aspichueta, Patricia, Joven, Jorge, Fernández-Real, José-Manuel, Quer, Juan Carlos, Valverde, Ángela M., Pardo, Albert, Vendrell, Joan, Ceperuelo-Mallafré, Victòria, and Fernández-Veledo, Sonia

Published
2023
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9. THU-290-YI Single nucleotide polymorphism analysis for predicting metabolic-associated fatty liver disease development in patients with severe obesity (types II and III)

Author

Jiménez-Aguilar, Juan Manuel, primary, Jiménez-Franco, Andrea, additional, Castañé, Helena, additional, Onoiu, Alina-Iuliana, additional, Cambra-Cortes, Vicente, additional, Placed-Gallego, Cristina, additional, Martínez-Navidad, Cristian, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2024
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10. THU-263-YI Significance of adipose tissue fibrosis and adipocyte in the progression of metabolic dysfunction-associated steatohepatitis in severe obesity patients

Author

Jiménez-Franco, Andrea, primary, Ramirez-Baños, Marina, additional, Placed-Gallego, Cristina, additional, Jiménez-Aguilar, Juan Manuel, additional, Martínez-Navidad, Cristian, additional, Castañé, Helena, additional, Onoiu, Alina-Iuliana, additional, Cambra-Cortes, Vicente, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2024
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11. THU-257 Metabolic profiling of adipose tissues in metabolic dysfunction-associated steatohepatitis (MASH): insights from lipidomic, proteomic, and epigenetic analyses in morbidly obese patients undergoing bariatric surgery

Author

Placed-Gallego, Cristina, primary, Jiménez-Aguilar, Juan Manuel, additional, Onoiu, Alina-Iuliana, additional, Cambra-Cortes, Vicente, additional, Jiménez-Franco, Andrea, additional, Martínez-Navidad, Cristian, additional, Castañé, Helena, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2024
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12. THU-250-YI Untargeted lipidomics unveils distinct signature of metabolic dysfunction-associated steatohepatitis in the context of obesity

Author

Onoiu, Alina-Iuliana, primary, Cambra-Cortes, Vicente, additional, Jiménez-Franco, Andrea, additional, Placed-Gallego, Cristina, additional, Jiménez-Aguilar, Juan Manuel, additional, Martínez-Navidad, Cristian, additional, Castañé, Helena, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2024
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13. Inferring propagation paths for sparsely observed perturbations on complex networks

Author

Massucci, Francesco Alessandro, Wheeler, Jonathan, Beltran-Debon, Raul, Joven, Jorge, Sales-Pardo, Marta, and Guimera, Roger

Subjects
Computer Science - Social and Information Networks, Physics - Physics and Society
Abstract

In a complex system, perturbations propagate by following paths on the network of interactions among the system's units. In contrast to what happens with the spreading of epidemics, observations of general perturbations are often very sparse in time (there is a single observation of the perturbed system) and in "space" (only a few perturbed and unperturbed units are observed). A major challenge in many areas, from biology to the social sciences, is to infer the propagation paths from observations of the effects of perturbation under these sparsity conditions. We address this problem and show that it is possible to go beyond the usual approach of using the shortest paths connecting the known perturbed nodes. Specifically, we show that a simple and general probabilistic model, which we solved using belief propagation, provides fast and accurate estimates of the probabilities of nodes being perturbed.

Published
2017
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17. Preliminary Metabolomics Study Suggests Favorable Metabolic Changes in the Plasma of Breast Cancer Patients after Surgery and Adjuvant Treatment.

Author

Jiménez-Franco, Andrea, Jiménez-Aguilar, Juan Manuel, Canela-Capdevila, Marta, García-Pablo, Raquel, Castañé, Helena, Martínez-Navidad, Cristian, Araguas, Pablo, Malavé, Bárbara, Benavides-Villarreal, Rocío, Acosta, Johana C., Onoiu, Alina Iuliana, Somaiah, Navita, Camps, Jordi, Joven, Jorge, and Arenas, Meritxell

Subjects
AMINO acid metabolism, METABOLIC reprogramming, CANCER chemotherapy, ENERGY metabolism, CANCER treatment
Abstract

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Retrospective Analysis of Clostridioides difficile Infection Rates and Outcomes in Hospitalized Patients during the COVID-19 Pandemic: A Unicenter Study in Reus, Spain

Author

Iftimie, Simona, primary, López-Azcona, Ana F., additional, Corchero-Valverde, Mireia, additional, Peralta-Vázquez, Antonio, additional, López-Cordón, Laia Revuelta, additional, García-Cervera, Carles, additional, Fernández-Domínguez, Luís Manuel, additional, Camps, Jordi, additional, Joven, Jorge, additional, and Castro, Antoni, additional

Published
2024
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21. Versatile electroanalytical bioplatforms for dimultaneous determination of cancer-related DNA 5-hethyl- and 5-hydroxymethyl-cytosines at global and gene-specific levels in human serum and tissues

Author

Povedano, Eloy, Ruiz-Valdepeñas Montiel, Víctor, Valverde, Alejandro, Navarro-Villoslada, Fernando, Yáñez-Sedeño, Paloma, Pedrero, María, Montero-Calle, Ana, Barderas, Rodrigo, Peláez-García, Alberto, Mendiola, Marta, Hardisson, David, Feliú, Jaime, Camps, Jordi, Rodríguez-Tomàs, Elisabet, Joven, Jorge, Arenas, Meritxell, Campuzano, Susana, Pingarrón, Jose M., Povedano, Eloy, Ruiz-Valdepeñas Montiel, Víctor, Valverde, Alejandro, Navarro-Villoslada, Fernando, Yáñez-Sedeño, Paloma, Pedrero, María, Montero-Calle, Ana, Barderas, Rodrigo, Peláez-García, Alberto, Mendiola, Marta, Hardisson, David, Feliú, Jaime, Camps, Jordi, Rodríguez-Tomàs, Elisabet, Joven, Jorge, Arenas, Meritxell, Campuzano, Susana, and Pingarrón, Jose M.

Abstract

This paper reports the preparation of versatile electrochemical biosensing platforms for the simple, rapid, and PCR-independent detection of the most frequent DNA methylation marks (5-methylcytosine, 5-mC, and/or 5-hydroxymethylcytosine, 5-hmC) both at global and gene-specific levels. The implemented strategies, relying on the smart coupling of immuno-magnetic beads (MBs), specific DNA probes and amperometric detection at screen-printed carbon electrodes (SPCEs), provided sensitive and selective determination of the target methylated DNAs in less than 90 min with a great reproducibility and demonstrated feasibility for the simultaneous detection of the same or different cytosine epimarks both at global level and in different loci of the same gene or in different genes. The bioplatforms were applied to determine global methylation events in paraffin-embedded colorectal tissues and specific methylation at promoters of tumor suppressor genes in genomic DNA extracted from cancer cells and paraffin-embedded colorectal tissues, and in serum without previous DNA extraction from cancer patients., Depto. de Química Analítica, Fac. de Ciencias Químicas, TRUE, pub

Published
2024

22. Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy.

Author

Murcia-Mejía, Mauricio, Canela-Capdevila, Marta, García-Pablo, Raquel, Jiménez-Franco, Andrea, Jiménez-Aguilar, Juan Manuel, Badía, Joan, Benavides-Villarreal, Rocío, Acosta, Johana C., Arguís, Mónica, Onoiu, Alina-Iuliana, Castañé, Helena, Camps, Jordi, Arenas, Meritxell, and Joven, Jorge

Subjects
STEREOTACTIC radiotherapy, NON-small-cell lung carcinoma, RECEIVER operating characteristic curves, PROGNOSIS, CANCER radiotherapy
Abstract

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Serum Levels of Arachidonic Acid, Interleukin-6, and C-Reactive Protein as Potential Indicators of Pulmonary Viral Infections: Comparative Analysis of Influenza A, Respiratory Syncytial Virus Infection, and COVID-19.

Author

Iftimie, Simona, Gabaldó-Barrios, Xavier, Penadés-Nadal, Joan, Canela-Capdevila, Marta, Piñana, Rubén, Jiménez-Franco, Andrea, López-Azcona, Ana F., Castañé, Helena, Cárcel, María, Camps, Jordi, Castro, Antoni, and Joven, Jorge

Subjects
RESPIRATORY syncytial virus infections, RESPIRATORY infections, VIRUS diseases, ARACHIDONIC acid, COMMUNICABLE diseases
Abstract

Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Differential Analysis of Lipoprotein and Glycoprotein Profiles in Bacterial Infections and Covid-19 Using Proton Nuclear Magnetic Resonance and Machine Learning

Author

Iftimie, Simona, primary, Amigó, Nuria, additional, Martínez-Micaelo, Neus, additional, López-Azcona, Ana F., additional, Martínez-Navidad, Cristian, additional, Castañé, Helena, additional, Jiménez-franco, Andrea, additional, Ribalta, Josep, additional, Parra, Sandra, additional, Castro, Antoni, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2024
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26. Metabolomics and triple-negative breast cancer: A systematic review

Author

Arenas, Meritxell, primary, Fargas-Saladié, Maria, additional, Moreno-Solé, Marta, additional, Moyano-Femenia, Lucía, additional, Jiménez-Franco, Andrea, additional, Canela-Capdevila, Marta, additional, Castañé, Helena, additional, Martínez-Navidad, Cristian, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2023
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27. Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss

Author

Jiménez-Franco, Andrea, primary, Castañé, Helena, additional, Martínez-Navidad, Cristian, additional, Placed-Gallego, Cristina, additional, Hernández-Aguilera, Anna, additional, Fernández-Arroyo, Salvador, additional, Samarra, Iris, additional, Canela-Capdevila, Marta, additional, Arenas, Meritxell, additional, Zorzano, Antonio, additional, Hernández-Alvarez, María Isabel, additional, Castillo, Daniel del, additional, Paris, Marta, additional, Menendez, Javier A., additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2023
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32. Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis

Author

Castañé, Helena, primary, Jiménez-Franco, Andrea, additional, Martínez-Navidad, Cristian, additional, Placed-Gallego, Cristina, additional, Cambra-Cortés, Vicente, additional, Perta, Adelina-Miruna, additional, París, Marta, additional, del Castillo, Daniel, additional, Arenas, Meritxell, additional, Camps, Jordi, additional, and Joven, Jorge, additional

Published
2023
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35. Silibinin is a direct inhibitor of STAT3

Author

Verdura, Sara, Cuyàs, Elisabet, Llorach-Parés, Laura, Pérez-Sánchez, Almudena, Micol, Vicente, Nonell-Canals, Alfons, Joven, Jorge, Valiente, Manuel, Sánchez-Martínez, Melchor, Bosch-Barrera, Joaquim, and Menendez, Javier A.

Published
2018
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36. 2837: Metabolic profiling of plasma and tissue in breast cancer patients: uncovering therapeutic response

Author

Jiménez-Franco, Andrea, Calderón, David, Jiménez-Aguilar, Juanma, Canela-Capdevila, Marta, García-Pablo, Raquel, Castañé, Helena, Araguas, Pablo, Malave, Bárbara, Acosta, Johana Cristina, Benavides, Rocío, Árquez, Miguel, Castaño, Fredy, Riu, Francesc, de la Flor, Miriam, Jordà, Coia, Melé, Mireia, Repkova, Jana, Amillano, Kepa, Camps, Jordi, Joven, Jorge, and Arenas, Meritxell

Published
2024
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43. Retrospective Analysis of Vaccination Status and Predominant Viral Variants in Patients Hospitalized with COVID-19 in Reus, Spain

Author

Iftimie, Simona, primary, López-Azcona, Ana F., additional, Lozano-Olmo, María José, additional, Naval-Ferrando, Àngels, additional, Domingo-Cortés, Vicent, additional, Castañé, Helena, additional, Jiménez-Franco, Andrea, additional, Hernández-Aguilera, Anna, additional, Guilarte, Carmen, additional, Riu, Francesc, additional, Camps, Jordi, additional, Joven, Jorge, additional, and Castro, Antoni, additional

Published
2023
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44. Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eusko Jaurlaritza, Instituto de Salud Carlos III, Fundación la Caixa, Universidad Rovira i Virgili, Diputación de Tarragona, Generalitat de Catalunya, European Commission, Centro de Investigación Biomédica en Red Cáncer (España), Ministerio de Ciencia e Innovación (España), Marsal-Beltran, Anna, Rodríguez-Castellano, Adrià, Astiarraga, Brenno, Calvo, Enrique, Rada, Patricia, Madeira, Ana, Rodríguez-Peña, M-Mar, Llauradó, Gemma, Núñez-Roa, Catalina, Gómez-Santos, Beatriz, Maymó-Masip, Elsa, Bosch, Ramón, Frutos, María Dolores, Moreno-Navarrete, José María, Ramos-Molina, Bruno, Aspichueta, Patricia, Joven, Jorge, Fernández-Real, José M., Quer, Juan Carlos, Valverde, Ángela M., Pardo, Albert, Vendrell, Joan, Ceperuelo-Mallafré, Victoria, Fernández-Veledo, Sonia, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Eusko Jaurlaritza, Instituto de Salud Carlos III, Fundación la Caixa, Universidad Rovira i Virgili, Diputación de Tarragona, Generalitat de Catalunya, European Commission, Centro de Investigación Biomédica en Red Cáncer (España), Ministerio de Ciencia e Innovación (España), Marsal-Beltran, Anna, Rodríguez-Castellano, Adrià, Astiarraga, Brenno, Calvo, Enrique, Rada, Patricia, Madeira, Ana, Rodríguez-Peña, M-Mar, Llauradó, Gemma, Núñez-Roa, Catalina, Gómez-Santos, Beatriz, Maymó-Masip, Elsa, Bosch, Ramón, Frutos, María Dolores, Moreno-Navarrete, José María, Ramos-Molina, Bruno, Aspichueta, Patricia, Joven, Jorge, Fernández-Real, José M., Quer, Juan Carlos, Valverde, Ángela M., Pardo, Albert, Vendrell, Joan, Ceperuelo-Mallafré, Victoria, and Fernández-Veledo, Sonia

Abstract

[Objective]: Succinate and succinate receptor 1 (SUCNR1) are linked to fibrotic remodeling in models of non-alcoholic fatty liver disease (NAFLD), but whether they have roles beyond the activation of hepatic stellate cells remains unexplored. We investigated the succinate/SUCNR1 axis in the context of NAFLD specifically in hepatocytes., [Methods]: We studied the phenotype of wild-type and Sucnr1−/− mice fed a choline-deficient high-fat diet to induce non-alcoholic steatohepatitis (NASH), and explored the function of SUCNR1 in murine primary hepatocytes and human HepG2 cells treated with palmitic acid. Lastly, plasma succinate and hepatic SUCNR1 expression were analyzed in four independent cohorts of patients in different NAFLD stages., [Results]. Sucnr1 was upregulated in murine liver and primary hepatocytes in response to diet-induced NASH. Sucnr1 deficiency provoked both beneficial (reduced fibrosis and endoplasmic reticulum stress) and detrimental (exacerbated steatosis and inflammation and reduced glycogen content) effects in the liver, and disrupted glucose homeostasis. Studies in vitro revealed that hepatocyte injury increased Sucnr1 expression, which when activated improved lipid and glycogen homeostasis in damaged hepatocytes. In humans, SUCNR1 expression was a good determinant of NAFLD progression to advanced stages. In a population at risk of NAFLD, circulating succinate was elevated in patients with a fatty liver index (FLI) ≥60. Indeed, succinate had good predictive value for steatosis diagnosed by FLI, and improved the prediction of moderate/severe steatosis through biopsy when added to an FLI algorithm., [Conclusions]. We identify hepatocytes as target cells of extracellular succinate during NAFLD progression and uncover a hitherto unknown function for SUCNR1 as a regulator of hepatocyte glucose and lipid metabolism. Our clinical data highlight the potential of succinate and hepatic SUCNR1 expression as markers to diagnose fatty liver and NASH, respectively.

Published
2023

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