Visceral Adipose Tissue and its Crosstalk With the Liver Allograft: Implications for Transplant Outcomes

Abstract

Liver transplantation (LT) is the definitive treatment for end-stage liver diseases such as hepatocellular carcinoma (HCC) or cirrhosis, in a clinical context increasingly influenced by the high prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease. Organ shortages have expanded the use of extended-criteria donor grafts, including steatotic livers from donors after brain death or cardiocirculatory death. However, graft steatosis remains a major risk factor for ischemia/reperfusion (I/R) injury, early allograft dysfunction, and posttransplant outcomes, and current protective strategies are insufficient to fully overcome these challenges. Visceral adipose tissue (VAT) is an active endocrine and immunometabolic organ that can shape systemic inflammation and immune tone. Clinical studies report an association between increased VAT and I/R injury, graft dysfunction, rejection, frailty, and HCC recurrence after LT, particularly in recipients with obesity and in recipients transplanted for cirrhosis and/or HCC. Under stress conditions, dysfunctional VAT shifts toward a proinflammatory phenotype characterized by altered secretion of cytokines, adipokines, chemokines, and lipid mediators. This review analyzes the role of the adipose tissue-liver axis in LT, with emphasis on how adipose-related mediators may modulate I/R injury and alloimmune responses in clinically relevant settings. We synthesize evidence from human cohorts and preclinical LT and warm I/R models, highlight major knowledge gaps related to tissue-source attribution and context-dependent mechanisms, and discuss emerging therapeutic strategies to modulate adipose tissue inflammation and immunometabolic signaling. Integrating adipose biology into LT research may help refine risk stratification and identify new avenues to improve graft utilization and long-term outcomes.