Z Gastroenterol 2014; 52 - P_3_08
DOI: 10.1055/s-0033-1360927

Effect of direct single-dose irradiation on fat metabolism in rat liver: FAT/CD36 as the main responsible protein?

G Martius 1, SM Alwahsh 1, M Rave-Fränk 2, CF Hess 2, H Christiansen 3, G Ramadori 1, IA Malik 1
  • 1University Medical Center Goettingen, Gastroenterology and Endocrinology, Goettingen, Germany
  • 2University Medical Center Goettingen, Radiotherapy and Radiooncology, Goettingen, Germany
  • 3Medical University Hannover, Radiotherapy and special oncology, Hannover, Germany

Introduction: The liver is a very radiosensitive organ in which processes are initiated early in time which can lead to impairment of liver function. Because the liver is the main metabolism organ of the body, it is necessary to characterize a negative impact on liver function triggered by radiation exposure. A rat model of acute Hepatosteatosis by single-dose liver irradiation was developed to examine histological changes and altered gene expression at early time points.

Methods: A single dose of 25 Gy was selectively given to rats with liver on focus. The rats were sacrificed humanly and liver organs were removed at different time points starting from 1 hour (latest is 48 hours). RNA and proteins were isolated to perform qPCR and Western Blot. Lipids were specifically stained in liver cryosections by Nile Red dye. Additionally the concentrations of different fat types were measured in serum and liver tissue of irradiated and sham-irradiated rats.

Results: The concentration of free fatty acids, triglycerides and total lipids increased in liver tissue after irradiation with maxima between 12 – 48 hours. At the same time HDL, cholesterol and triglyceride concentration decreased in serum after irradiation at the corresponding time points. It was seen by fluorescent Nile Red staining that fat is accumulating in vivo within cytoplasm of hepatocytes forming vacuoles, clearly visible from 12 hours after irradiation. The vacuoles increased up to 48 hours of examination. The transmembrane transport protein FAT/CD36 (fatty acid translocase/cluster of differentiation 36) was the highest upregulated among all others shown by real time PCR and Western Blot.

Conclusion: Impaired liver metabolism and effect of radiotherapy suggest readjusting the combination of chemotherapy and radiotherapy. The accumulation of fatty acids is probably due to a highly upregulated import of fatty acids by FAT/CD36. It can be assumed that cells will not show fat accumulation when FAT/CD36 is inhibited. This can lead to therapy attempts to treat hepatic steatosis during or after thoracic radiation treatment.