Abstract
BACKGROUND: Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure, yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae, with obesity emerging as a critical clinical challenge. AIM: To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological, behavioral, and molecular perspectives, thereby providing a foundation for targeted interventions. METHODS: We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025. The search strategy incorporated terms including "obesity", "overweight" and "post organ transplantation". Only randomized controlled trials, meta-analyses, and systematic reviews were included. Non-empirical publications and irrelevant studies were excluded. Data extraction and quality assessment were performed by two independent reviewers, with disagreements resolved by a third researcher. RESULTS: A total of 1457 articles were initially identified, of which 146 met the inclusion criteria. These studies encompassed liver, kidney, heart, and lung transplant recipients. Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia, insulin resistance, and dyslipidemia. Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance. At the molecular level, immunosuppressants disrupt adipokine signaling (e.g., leptin and adiponectin), induce inflammatory and oxidative stress responses, and activate adipogenic pathways leading to lipid accumulation. CONCLUSION: Post-transplant obesity arises from a complex interplay of pharmacological, behavioral, and molecular factors. A multidisciplinary approach-incorporating pharmacological modification, nutritional management, physical activity, and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes. Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.