Immune–Metabolic Dysfunction in MASLD: Biomarkers and Therapeutic Modulation

Metabolic dysfunction–associated steatotic liver disease (MASLD) emerges from a tightly interwoven network of immune and metabolic disturbances that drive steatosis, inflammation, fibrosis progression, and extrahepatic complications. This project delineates the bidirectional crosstalk between hepatocyte lipid handling, mitochondrial stress, and innate/adaptive immune activation—focusing on pathways such as lipotoxicity, oxidative stress, inflammasome signaling (e.g., NLRP3), gut–liver axis perturbations, and cytokine/chemokine networks that perpetuate hepatic injury.We aim to:Identify and validate multimodal biomarkers that capture immune–metabolic activity across the MASLD spectrum, integrating serum proteins (e.g., keratin-18, cytokines), lipidomic and metabolomic signatures, cell-free nucleic acids, and microbiome-derived metabolites with imaging (e.g., MRI-PDFF, elastography) and machine-learning–based composite scores.Map patient endotypes using systems biology to improve risk stratification and predict therapeutic response.Evaluate therapeutic strategies that modulate immune–metabolic circuits, including lifestyle and dietary interventions, GLP-1/GIP receptor agonists, FGF21 analogs, PPAR and THR-β agonists, SGLT2 inhibitors, and anti-inflammatory/anti-fibrotic approaches (e.g., CCR2/CCR5 blockade, inflammasome inhibitors), as well as combination regimens.By integrating deep phenotyping with mechanistic insights, this research seeks to establish actionable biomarkers and targeted interventions that personalize care, prevent progression to steatohepatitis and advanced fibrosis, and reduce cardiometabolic risk in MASLD. Topic editors: Rakesh Kumar Jagdish, Hongjun Yu, Yuanyue Zhu Source: https://www.frontiersin.org/research-topics/75382/immune-metabolic-dysfunction-in-masld-biomarkers-and-therapeutic-modulation