MINI REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1693753
This article is part of the Research TopicMolecular Insights into Fatty Liver Disease: Pathogenesis, Progression, and Therapeutic StrategiesView all 6 articles
Immunometabolic Integration in Therapeutic Strategies for Managing MASLD
Provisionally accepted
- 1University of Rovira i Virgili, Tarragona, Spain
- 2Universitat Rovira i Virgili, Tarragona, Spain
- 3Institut d'Investigacio Sanitaria Pere Virgili, Reus, Spain
- 4Hospital Universitari Sant Joan de Reus, Reus, Spain
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is clinically complex. Management approaches have focused on addressing the traits of metabolic syndrome and promoting weight loss. However, current treatment options are inadequate, leaving key disease-driving factors unaddressed. Evidence suggests that immune dysregulation determines disease trajectory. Metabolic pathways shape the immune landscape, and the immune system influences metabolic homeostasis. Developing therapies that integrate metabolic correction with immune restoration is essential. We review current available strategies and discuss areas where further research is needed to design drugs and therapeutic combinations that mitigate the complex metabolic and inflammatory interactions driving obesity-associated chronic liver disease. The immunomodulatory effects of obesity-focused interventions remain poorly understood. Bariatric surgery and incretin-based therapies can reduce body fat while reprogramming the hepatic immune environment. Metabolic modulators can reduce lipotoxicity, suppress harmful cytokine networks, and promote reparative immune responses. Other strategies include blocking danger-signaling pathways, modulating chemokine axes, and using cellular therapies. The goal is to interrupt pro-inflammatory amplification cascades and preserve reparative immune cell populations, redefining therapeutic possibilities for liver diseases. Despite advancements in the field, uncertainties still exist regarding the immunometabolic integration. Ongoing clinical trials and the recent approval of two drugs for treating this condition will provide valuable real-world insights in the future about the long-term safety and effectiveness of potentially more accurate treatment approaches. Moreover, causal and clinical biomarkers are being investigated to enhance the diagnosis and management of the significant challenges associated with MASLD-related cirrhosis. Prioritizing and initiating treatment earlier are key factors for achieving successful outcomes.
Keywords: Genetics, GLP-1, Inflammation, Lipid Metabolism, MASH, Mitochondrial dysfunction, Obesity, pharmacotherapies
Received: 27 Aug 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 González Serrano, Onoiu, Camps and Joven. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sergio González Serrano, sergio.gonzalez@estudiants.urv.cat
Jorge Joven, jorge.joven@salutsantjoan.cat
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