Irradiated obese adipocytes are prone to oxidative stress, inflammation, senescence, and fibrosis

Abstract

Abstract Cancer patients with obesity who undergo radiotherapy are more likely to suffer from side effects caused by the radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal tissues during radiation treatment results in post-irradiation related chronic damage leading to fibrosis. Obese adipose tissue is associated with oxidative stress promoting oxidative damage, senescence, inflammation, and fibrosis. However, the effect that radiation has on obese adipose tissue during the radiation treatment is unknown. In the present work, to study the obese conditions we utilized 3T3-L1 adipocytes exposed to fatty acid cocktail for an in vitro model and C57/BL/6 mice exposed to high fat diet (HFD) for an in vivo obese model. We established a clinically relevant dosing model of pelvic radiation of 7.5 Gy, 1.2 Gy/min, 160 KV X-ray over 5 days to analyze the effect of radiation in the context of obesity for both models. We found that obese and irradiated obese adipose released free fatty acid and glycerol (1–2 fold compared to control) and this was accompanied by elevated (2–3 fold compared to control) oxidative damage in vitro and in vivo. Irradiated HFD adipose displayed high oxidative stress, senescence, inflammation, and fibrosis as compared to obesity alone, which may induce cancer progression and recurrence.