Sex Differences of Radiation Damage in High-Fat-Diet-Fed Mice and the Regulatory Effect of Melatonin

The consumption of a high-fat diet (HFD) and exposure to ionizing radiation (IR) are closely associated with many diseases. To evaluate the interaction between HFDs and IR-induced injury, we gave mice whole abdominal irradiation (WAI) to examine the extent of intestinal injury under different dietary conditions. Melatonin (MLT) is a free radical scavenger that effectively prevents hematopoietic, immune, and gastrointestinal damage induced by IR. However, its effects on WAI-induced intestinal injury in HFD-fed mice remain unclear. We demonstrated that MLT can promote intestinal structural repair following WAI and enhance the regeneration capacity of Lgr5⁺ intestinal stem cells. In addition, we investigated the effects of radiation damage on sexual dimorphism in HFD-fed mice. The results showed that the degree of IR-induced intestinal injury was more severe in the HFD-fed female mice. MLT preserved the intestinal microbiota composition of HFD-fed mice and increased the abundance of Bacteroides and Proteobacteria in male and female mice, respectively. In conclusion, MLT may reduce the negative effects of HFD and IR, thereby providing assistance in preserving the structure and function of the intestine.