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Updated: Sep 18, 2025

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis
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Radiation Promotes Acute and Chronic Damage to Adipose Tissue.

Kia T Liermann-Wooldrik1, Elizabeth A Kosmacek1, Joshua A McDowell1

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

International Journal of Molecular Sciences
|June 26, 2025
PubMed
Summary

Radiation therapy damages fat cells, causing oxidative stress, inflammation, and metabolic dysfunction. This chronic damage may worsen treatment toxicity and cancer progression, highlighting the need for adipose tissue protection.

Keywords:
adipose tissueinflammationmetabolismoxidative stressradiationsenescence

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Area of Science:

  • Oncology
  • Metabolic Science
  • Radiation Biology

Background:

  • Radiotherapy is a cornerstone of cancer treatment, but its effects on adipose tissue are not well understood.
  • Adipose tissue is frequently exposed to radiation, yet its damage and long-term consequences remain largely unelucidated.
  • Existing research on radiation's impact on adipose tissue often involves whole-body irradiation, not clinically relevant doses.

Purpose of the Study:

  • To investigate the acute and persistent damage to adipocytes following clinically relevant radiation doses.
  • To elucidate the molecular and cellular changes in adipose tissue after radiation exposure.
  • To explore the potential link between radiation-induced adipose tissue dysfunction and cancer progression.

Main Methods:

  • In vitro and in vivo experiments using adipocytes and animal models.
  • Assessment of reactive oxygen species (ROS), lipid peroxidation, and lipolytic activity.
  • RNA sequencing to analyze gene expression changes, focusing on senescence and inflammation pathways.
  • In vivo analysis of immune cell infiltration (macrophages, T-cells) at 1 and 6 months post-irradiation.

Main Results:

  • Irradiated adipocytes exhibited increased ROS, lipid peroxidation, and lipolysis compared to controls.
  • RNA sequencing revealed upregulation of senescence and inflammation pathways in irradiated adipose tissue.
  • In vivo models showed increased macrophage and T-cell accumulation in adipose tissue 1 and 6 months after radiation exposure.
  • Observed changes in irradiated adipose tissue mirror those seen in obesity, a known cancer driver.

Conclusions:

  • Clinically relevant radiation doses induce significant acute and chronic damage in adipocytes.
  • Radiation exposure triggers oxidative stress, metabolic dysfunction, inflammation, and senescence in adipose tissue.
  • Protecting adipose tissue during radiotherapy may mitigate treatment toxicity and potentially reduce cancer recurrence and progression.