Surgery, Medicine, Anatomy, Nutrition and Dietetics
20
Scopus Publications
Scopus Publications
Platelet-Activating Factor Pathway in Women With Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity Joan Duran‐Bertran, Helena Clavero‐Mestres, Razieh Mahmoudian, Sara Muñiz‐Piera, Carmen Aguilar, David Riesco, Javier Camaron, Salomé Martínez, Margarida Vives, Marta París, Fàtima Sabench, Teresa Auguet Obesity, 2026 Objective This study aimed to investigate the platelet‐activating factor (PAF) pathway in obesity‐associated metabolic dysfunction‐associated steatotic liver disease (MASLD) by evaluating hepatic expression of the PAF receptor ( PAFR ) and circulating levels of lipoprotein‐associated phospholipase A2 (Lp‐PLA2) across different stages of disease severity. Methods Liver biopsies and blood samples were collected from 64 women with severe obesity undergoing bariatric surgery. Hepatic PAFR mRNA expression was quantified by qRT‐PCR, and plasma Lp‐PLA2 concentrations were measured using ELISA. Histological evaluation of MASLD and metabolic dysfunction‐associated steatohepatitis (MASH) was performed according to established criteria. Associations between biochemical, histological, and molecular parameters were analyzed using appropriate statistical tests. Results Hepatic PAFR expression was significantly upregulated in MASLD, with the highest levels observed in patients with MASH. PAFR expression correlated positively with key histological features, including steatosis, lobular inflammation, and hepatocyte ballooning. In contrast, circulating Lp‐PLA2 levels did not differ across MASLD stages and showed no correlation with hepatic PAFR expression or with liver injury markers. Conclusions The PAF‐PAFR axis is upregulated in obesity‐associated MASLD and is strongly linked to inflammatory and injury‐related histological features, supporting PAFR as a potential therapeutic target. Conversely, plasma Lp‐PLA2 does not appear to be a reliable noninvasive biomarker of MASLD severity in women with obesity. image
Multi-omics profiling reveals altered mitochondrial metabolism in adipose tissue from patients with metabolic dysfunction-associated steatohepatitis Helena Castañé, Andrea Jiménez-Franco, Anna Hernández-Aguilera, Cristian Martínez-Navidad, Vicente Cambra-Cortés, Alina-Iuliana Onoiu, Juan Manuel Jiménez-Aguilar, Marta París, Mercè Hernández, David Parada, Carmen Guilarte, Antonio Zorzano, María Isabel Hernández-Alvarez, Jordi Camps, Jorge Joven Ebiomedicine, 2025 BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form steatohepatitis (MASH) contribute to rising morbidity and mortality rates. The storage of fat in humans is closely associated with these diseases' progression. Thus, adipose tissue metabolic homeostasis could be key in both the onset and progression of MASH. METHODS: We conducted a case-control observational research using a systems biology-based approach to analyse liver, abdominal subcutaneous adipose tissue (SAT), omental visceral adipose tissue (VAT), and blood of n = 100 patients undergoing bariatric surgery (NCT05554224). MASH was diagnosed through histologic assessment. Whole-slide image analysis, lipidomics, proteomics, and transcriptomics were performed on tissue samples. Lipidomics and proteomics profiles were determined on plasma samples. FINDINGS: Liver transcriptomics, proteomics, and lipidomics revealed interconnected pathways associated with inflammation, mitochondrial dysfunction, and lipotoxicity in MASH. Paired adipose tissue biopsies had larger adipocyte areas in both fat depots in MASH. Enrichment analyses of proteomics and lipidomics data confirmed the association of liver lesions with mitochondrial dysfunction in VAT. Plasma lipidomics identified candidates with high diagnostic accuracy (AUC = 0.919, 95% CI 0.840-0.979) for screening MASH. INTERPRETATION: Mitochondrial dysfunction is also present in VAT in patients with obesity-associated MASH. This may cause a disruption in the metabolic equilibrium of lipid processing and storage, which impacts the liver and accelerates detrimental adaptative responses. FUNDING: The project leading to these results has received funding from 'la Caixa' Foundation (HR21-00430), and from the Instituto de Salud Carlos III (ISCIII) (PI21/00510) and co-funded by the European Union.
Glutaminolysis-induced mTORC1 activation drives non-alcoholic steatohepatitis progression Noemí Cabré, Fedra Luciano-Mateo, Douglas J. Chapski, Gerard Baiges-Gaya, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Helena Castañé, Elisabet Rodríguez-Tomàs, Marta París, Fàtima Sabench, Daniel Del Castillo, Josep M. del Bas, Mercedes Tomé, Clément Bodineau, Alejandro Sola-García, José López-Miranda, Alejandro Martín-Montalvo, Raúl V. Durán, Thomas M. Vondriska, Manuel Rosa-Garrido, Jordi Camps, Javier A. Menéndez, Jorge Joven Journal of Hepatology, 2025
Metabolic-Associated Fatty Liver Disease and Weight Loss After Bariatric Surgery: A Systematic Review and Meta-Analysis Fatima Sabench, Elena Cristina Rusu, Helena Clavero-Mestres, Vicente Arredondo-Prats, Marina Veciana-Molins, Sara Muñiz-Piera, Margarita Vives, Carmen Aguilar, Elia Bartra, Marta París-Sans, Ajla Alibalic, Maria Teresa Auguet Quintillà Obesity Surgery, 2024 Background Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) are increasingly prevalent in patients undergoing bariatric surgery (BS). Understanding their impact on weight loss outcomes after surgery and highlighting the results of surgical techniques such as Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) in relation to the presence of MASH are essential for improving patient management and predicting long-term success. Methods A systematic review and meta-analysis were conducted. We searched the PubMed database; inclusion criteria were BS patients with liver impairment data at surgery and weight loss data at follow-up of 6 months or longer. Meta-analyses were conducted using R’s meta package, assessing heterogeneity with the I2 statistic and employing subgroup analyses where necessary. Results Out of 1126 eligible studies, 22 were included in the final systematic review. For the MASLD vs. Normal Liver (NL) comparison, no significant difference in BMI change was found at 12 months, but subgroup analysis indicated a possible publication bias (published data vs data collected). In the MASH vs. non-MASH comparison, high heterogeneity was noted at 12 months, and further stratification by surgical technique revealed that SG patients with MASH experienced lower weight loss, approaching statistical significance. Conclusions MASLD does not significantly affect short-term weight loss outcomes post-BS, but long-term results show variability. Standardized reporting practices and complete data dissemination are essential for future research to enhance meta-analysis reliability and generalizability. Graphical Abstract
Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss Andrea Jiménez-Franco, Helena Castañé, Cristian Martínez-Navidad, Cristina Placed-Gallego, Anna Hernández-Aguilera, Salvador Fernández-Arroyo, Iris Samarra, Marta Canela-Capdevila, Meritxell Arenas, Antonio Zorzano, María Isabel Hernández-Alvarez, Daniel del Castillo, Marta Paris, Javier A. Menendez, Jordi Camps, Jorge Joven Clinical Nutrition, 2024
Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis Helena Castañé, Andrea Jiménez-Franco, Cristian Martínez-Navidad, Cristina Placed-Gallego, Vicente Cambra-Cortés, Adelina-Miruna Perta, Marta París, Daniel del Castillo, Meritxell Arenas, Jordi Camps, Jorge Joven Antioxidants, 2023 Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = −0.24, p < 0.001, and rho = −0.30, p < 0.001, respectively) and body mass index (rho = −0.15, p = 0.001, and rho = −0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.
The Role of Olfactomedin 2 in the Adipose Tissue–Liver Axis and Its Implication in Obesity-Associated Nonalcoholic Fatty Liver Disease Andrea Barrientos-Riosalido, Laia Bertran, Mercè Vilaró-Blay, Carmen Aguilar, Salomé Martínez, Marta Paris, Fàtima Sabench, David Riesco, Jessica Binetti, Daniel Del Castillo, Cristóbal Richart, Teresa Auguet International Journal of Molecular Sciences, 2023 This study’s objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue–liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT–qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.
Laparoscopic Sleeve Gastrectomy in Patients with Severe Obesity Restores Adaptive Responses Leading to Nonalcoholic Steatohepatitis Noemí Cabré, Fedra Luciano-Mateo, Douglas J. Chapski, Gerard Baiges-Gaya, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Helena Castañé, Elisabet Rodríguez-Tomàs, Marta París, Fàtima Sabench, Daniel Del Castillo, Josep M. del Bas, Mercedes Tomé, Clément Bodineau, Alejandro Sola-García, José López-Miranda, Alejandro Martín-Montalvo, Raúl V. Durán, Thomas M. Vondriska, Manuel Rosa-Garrido, Jordi Camps, Javier A. Menéndez, Jorge Joven International Journal of Molecular Sciences, 2022 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.
Nonalcoholic Steatohepatitis Modifies Serum Iron-Related Variables in Patients with Morbid Obesity Anna Hernández-Aguilera, Núria Casacuberta, Helena Castañé, Montserrat Fibla, Salvador Fernández-Arroyo, Isabel Fort-Gallifa, Marta París, Fàtima Sabench, Daniel Del Castillo, Gerard Baiges-Gaya, Elisabet Rodríguez-Tomàs, Teresa Sans, Jordi Camps, Jorge Joven Biological Trace Element Research, 2021
Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis Noemí Cabré, Fedra Luciano‐Mateo, Gerard Baiges‐Gayà, Salvador Fernández‐Arroyo, Elisabet Rodríguez‐Tomàs, Anna Hernández‐Aguilera, Marta París, Fàtima Sabench, Daniel Del Castillo, José López‐Miranda, Javier A. Menéndez, Jordi Camps, Jorge Joven Alimentary Pharmacology and Therapeutics, 2020
