The role of obesity as an immunometabolic factor in tissue and cell transplantation

Abstract

Background. Obesity has a critical global public health challenge, characterized by excessive accumulation of adipose tissue and a state of chronic systemic inflammation that disrupts metabolism and immune function. The low-grade inflammation and immunometabolic dysfunction typical of obesity involve an imbalance of adipokines and pro-inflammatory cytokines, which can affect host immune responses and graft tolerance after transplantation. In this context, the molecular mechanisms of obesity, including activation of the NF-кB pathway and insulin resistance, may influence both graft survival and the risk of rejection. The aim of the study is to evaluate the role of obesity as an immunometabolic determinant of tissue and cell transplant success. Material and Methods. Articles from the MDPI, PubMed, Researcher, NCBI, WILEY, Science Direct databases published between 2020 and 2026 were analyzed. Observational studies and systematic reviews were included to estimate current evidence about the impact of obesity on the immunometabolic homeostasis in the context of tissue and cell transplantation. Results. Current evidence suggests that the inflammatory and immunometabolic status associated with obesity correlates with significant alterations in the post-transplant microenvironment. Elevated levels of TNF-α, IL-6, and leptin, together with decreased adiponectin, have been associated with persistent activation of the NF-κB pathway and amplification of the proinflammatory immune response, promoting increased allo-reactivity of T lymphocytes and reduced regulatory T cell function. This proinflammatory immune polarization contributes to enhanced acute rejection and progression of chronic rejection. Furthermore, insulin resistance has been linked to endothelial dysfunction, increased oxidative stress, and impaired angiogenesis in the transplanted tissue, with affecting graft perfusion and integration. A microenvironment characterized by excess reactive oxygen species and mitochondrial dysfunction promotes activation of apoptotic pathways and fibrotic remodeling of the transplanted tissue, mechanisms involved in reduced long-term graft survival. Conclusion. In the case of cellular transplantation, the obesity-associated proinflammatory state has been correlated with decreased engraftment rates. Overall, these biochemical and immunometabolic changes support the association between obesity and an increased risk of post-transplant complications, rejection, and graft loss.