Radiation Promotes Acute and Chronic Damage to Adipose Tissue

Radiotherapy is commonly used for treating various types of cancer. In addition, adipose tissue is not routinely spared during typical radiation treatment. Although radiation is known to induce metabolic effects in patients, the effects of radiation therapy on adipose tissue have not been elucidated. Currently, few studies have investigated the impact of radiation exposure on adipose tissue, and these have primarily involved whole-body irradiation. This study aimed to understand the acutely persistent damage caused by clinically relevant radiation doses in adipocytes. Specifically, in vitro and in vivo, irradiated adipocytes increased reactive oxygen species (ROS) and lipid peroxidation levels and elevated lipolytic activity compared to unirradiated adipocytes. RNA sequencing also revealed the upregulation of senescence and inflammation pathways. We observed an increase in macrophage and T-cell accumulation at both 1 and 6 months after radiation exposure using in vivo models. Many of the changes observed in irradiated adipose tissue, including oxidative stress, metabolic dysfunction, inflammation, and senescence, are consistent with those observed in adipose tissue from obese patients, in which obesity is a known driver of many cancers. As adipose tissue damage is maintained chronically, protecting adipose tissue from the harmful effects of radiation exposure may improve radiation-induced toxicity and reduce cancer recurrence and progression.