What is the clinical evidence from this study?

Study design: Other. Population: Obesity and radiation-induced tissue damage (n=30). Intervention: Pelvic radiation vs. No irradiation (0 Gy). Primary outcome: Oxidative damage, senescence, inflammation, and fibrosis.

What does this research mean for the field?

Pelvic radiation of obese adipose tissue increases free fatty acid and glycerol release by 1-2 fold and elevates oxidative damage by 2-3 fold compared to control, exacerbating inflammation, senescence, and fibrosis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

November 13, 2025Scientific Reports1 citationsOpen Access

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

STSimran TakkarUniversity of Nebraska Medical Center EKElizabeth A. KosmacekNebraska Medical Center JMJoshua A. McDowellUniversity of Nebraska Medical Center

Key Result

Pelvic radiation of obese mice increased free fatty acid and glycerol release by 1-2 fold and elevated oxidative damage by 2-3 fold compared to control, promoting inflammation and fibrosis.

Structured PICO

Population

In vitro model using 3T3-L1 adipocytes exposed to a fatty acid cocktail, and an in vivo model using C57/BL/6 mice fed a high-fat diet (HFD) for 16 weeks.

Intervention

Pelvic radiation (7.5 Gy, 1.2 Gy/min, 160 KV X-ray over 5 days for mice; 3 fractions of 3 Gy for 3 days for cells).

Comparator

Normal diet (ND) mice with/without radiation, and HFD mice without radiation. Undifferentiated or normal 3T3-L1 cells without radiation.

Outcome

Levels of oxidative stress (8-OHdG, 4-HNE), senescence (p53, p21, p16), inflammation (macrophages, CD4+, CD8+ T cells, NF-kB), and fibrosis (α-SMA, TGF-β) in adipose tissue.surrogate

Radiation exacerbates oxidative stress, senescence, inflammation, and fibrosis in obese adipose tissue, highlighting a potential mechanism for increased normal tissue damage in obese patients undergoing radiotherapy.

Limitations

Only used 3T3 cells for in vitro experiments
Experiments were performed only in male C57/BL/6 mice
No potential differences between mouse and human adipose radiation responses were evaluated
Only focused on white adipose tissue (WAT)
Systemic metabolic changes may act as confounding factors
Did not evaluate effects on tumors
Only evaluated tissue-specific effects at a single time point (two months post-radiation)
Observational study design cannot establish cause and effect

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.

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