Impact of a Short-Term High-Fat Diet on Lifespan and Tumorigenesis After Early-Life Exposure to Radiation

Introduction: Children are highly susceptible to radiation's carcinogenic effects. Lifestyle, in particular, diet-induced obesity (DIO) is closely linked to cancer risk factors. Most prior studies, however, have concentrated on the impact of long-term lifestyle factors. Objective: We assessed the impact of a short-term, high-fat diet (HFD) during young or adult on lifespan shortening and tumor development after infant radiation exposure. Methodology: B6C3F1 male mice were irradiated at 1 week of age with 4 Gy of gamma rays or did not undergo irradiation (0 Gy). After weaning, they were assigned to HFD or normal-fat diet (NFD) for four weeks during young (4-8 weeks old) or adult (20-24 weeks old) stages. Body weight measurement, plasma biochemical analysis, lifespan analysis, and histopathological analysis for tumor diagnosis were carried out. Results: A temporary gain of body weight and hyperlipidemia were observed in mice fed the HFD. Although short-term HFD intake had limited impact on lifespan shortening and tumor development, a short-term HFD at a young age significantly increased spontaneous hepatocellular carcinoma (HCC) risk. Conclusion: The influence of a short-term HFD on DIO-associated cancer, such as HCC, should be specifically noted. Lifestyle normalization has potential for reducing cancer risk.