Radiation promotes acute and chronic damage to adipose tissue

Radiotherapy is a commonly used therapy for treating various cancer types. In addition, adipose tissues are not routinely spared during typical radiation treatments. Although radiation is known to induce metabolic effects in patients, the impact that radiation therapy has on adipose tissue has not been elucidated. Currently, there are few studies investigating 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 that clinically relevant radiation dosing causes to adipocytes. Specifically, in vitro and in vivo, irradiated adipocytes had increased reactive oxygen species (ROS) and lipid peroxidation levels and elevated lipolytic activity compared to unirradiated adipocytes. RNA sequencing also identified the upregulation of senescence and inflammation pathways. We observed an increase in macrophage and T-cell accumulation both 1 month and 6 months after radiation exposure using in vivo models. Many of the observed changes to 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. Because 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. Mice were pelvically irradiated receiving 7.5 Gy for 5 days. Primary mouse gonadal adipose tissue was harvested two months after radiation. Fat pads were digested with collagenase and incubated at 37 °C for 45 minutes, with manual swirling every 5 minutes. Once the fat was dissociated, 4x volume of cold HBSS (without Ca2+ & Mg 2+) was added and the tube was centrifuged at 450 g for 3 minutes at 4 °C. Mature adipocytes found in the floating fraction were removed and maintained in culture for 3 days.