Adipose tissue: an overlooked target of medical ionizing radiation and its metabolic consequences

Despite extensive research on radiation effects on various tissues, the impact on adipose tissue remains largely unexplored. This represents a critical knowledge gap given adipose tissue's role as an active endocrine organ and the extensive use of ionizing radiation in medical procedures. This review synthesizes the current evidence regarding the effects of ionizing radiation on adipose tissue pathophysiology, examining molecular mechanisms and clinical implications for metabolic health. We comprehensively reviewed studies investigating radiation effects on adipocytes and adipose-derived stem cells (ADSCs), analyzing different radiation energies, dose rates, and exposure timeframes. Converging evidence demonstrates that different dose protocols with ionizing radiation induce heterogeneous effects on adipose tissue cell number and size, pro-inflammatory secretome, and ADSCs functionality. Clinical studies in childhood cancer survivors reveal strong associations between abdominal radiation exposure and subsequent metabolic dysregulation, including insulin resistance and diabetes. Mechanistic studies suggest radiation-induced oxidative stress, impaired adipogenesis, and altered adipokine secretion as key pathways. Overall, ionizing radiation disrupts adipose tissue function through multiple molecular pathways, potentially predisposing individuals to long-term endocrine and metabolic dysfunctions. Elucidating the underlying mechanisms will contribute to optimize radiation therapy protocols and guide the development of targeted strategies to preserve metabolic health.