| In recent years,the incidence of head and neck tumors has increased significantly.As the main means to control tumor development and avoid cancer recurrence,radiotherapy has become increasingly prominent in the treatment of head and neck tumors.However,patients undergoing radiotherapy often have side effects such as weight loss and poor appetite,which increase the risk of diabetes and other metabolic diseases.The mechanism is not well understood.In addition,as the proportion of obese people has increased year by year,previous studies have found that whole body radiation aggravates insulin resistance induced by high-fat diet(HFD),it is thought that nutritional rapport is crucial in the context of radiotherapy or exposure.Objectives: To observe the effects of single head-neck irradiation intervention on the body weight,food intake and blood glucose of mice on chow diet(CD)and HFD;To explore the role of thyroid hormones,uncoupling protein 1(UCP1)in brown adipose tissue(BAT),glucose transporter 2(GLUT2)in liver in the effects of single head-neck irradiation intervention on energy metabolism in mice on CD and HFD.Methods: 10-week-old adult male C57BL/6 mice were randomly divided into four groups,non-irradiation(Ctrl)+CD group,irradiation(Irr)+CD group,Ctrl+HFD group,and Irr+HFD group.Irradiation mice were irradiated on the head and neck with a single dose of 6Gy X-ray after anesthesia,and non-irradiated mice were sham-treated.Then,according to the grouping,they were fed with CD or HFD for 10 weeks.During this period,the body weight,accumulated food intake at night,and glucose tolerance test were measured regularly to observe and evaluate the effects of single head-neck irradiation intervention on the metabolism of mice on CD and HFD.After that,we measured the levels of thyroid-stimulating hormone(TSH)and thyroid hormone T3 by enzyme linked immunosorbent assay(ELISA),and observed the morphology of thyroid follicule,brown adipocytes and white adipocytes by hematoxylin-eosin(HE)staining method.We also detected BAT UCP1 and liver GLUT2 by western blot(WB)to explore possible molecular mechanism of single head-neck irradiation intervention affected metabolic function in mice on CD and HFD.Results:(1)After single head-neck irradiation intervention,the weight of mice on a CD was relatively stable within 10 weeks,while the weight of mice on a HFD continued to increase within 10 weeks,single head-neck irradiation intervention significantly reduced the body weight of mice on HFD,especially from the 7th week after irradiation(Irr+HFD group vs.Ctrl+HFD group:(22.825 ± 0.619)g vs.(24.571 ± 0.422)g,P < 0.05,(23.163 ± 0.687)g vs.(25.171 ± 0.474)g,P < 0.05,(23.213 ± 0.699)g vs.(25.143 ± 0.501)g,P < 0.05,(23.388± 0.629)g vs.(25.286 ± 0.487)g,P < 0.05),but in mice on a CD,single head-neck irradiation intervention did not cause significant changes;(2)In HFD mice,single head-neck irradiation intervention significantly increased the weight of the cumulative food intake for 1hour,2 hours,3 hours,4 hours,6 hours,and 12 hours at night(Irr+HFD group vs.Ctrl+HFD group:(1.486 ± 0.153)g vs.(0.917 ± 0.079)g,P < 0.05,(1.914 ± 0.179)g vs.(1.267 ± 0.141)g,P < 0.05),in CD mice,single head-neck irradiation intervention did not cause significant changes;(3)In HFD mice,the calorie of the nocturnal cumulative food intake for 1 hour,2hours,3 hours,4 hours,5 hours,6 hours and 12 hours had increased significantly after single head-neck irradiation intervention(Irr+HFD group vs.Ctrl+HFD group:(5703.903 ± 694.733)k J vs.(3623.767 ± 313.222)k J,P < 0.05,(7511.080 ± 747.085)k J vs.(5007.387 ± 555.952)k J,P < 0.05),in CD mice,single head-neck irradiation intervention did not cause significant changes;(4)Thyroid follicles showed an irregular structure and were devoid of colloid in Irr+CD group and Ctrl+HFD group,single head-neck irradiation intervention restored the abnormal thyroid follicles caused by the HFD.In HFD mice,single head-neck irradiation intervention significantly increased the levels of T3 and TSH(Irr+HFD group vs.Ctrl+HFD group:(9.267 ± 0.666)pmol/L vs.(7.241 ± 0.246)pmol/L,P < 0.05,(11.010 ± 0.327)m U/L vs.(8.643 ± 0.238)m U/L,P < 0.05),however,in CD mice,single head-neck irradiation intervention did not cause significant changes in the levels of T3 and TSH;(5)In HFD mice,single head-neck irradiation intervention significantly increased the number of brown fat cells per unit area(Irr+HFD group vs.Ctrl+HFD group:(111.000 ± 10.336)vs.(80.750 ±4.905),P < 0.05),single head-neck irradiation intervention also significantly increased the expression of UCP1 in BAT(Irr+HFD group vs.Ctrl+HFD group:(1.838 ± 0.203)vs.(1.250 ± 0.255),P < 0.05),however,in CD mic,single head-neck irradiation intervention had no obvious effect on the number of brown fat cells per unit area and the expression of UCP1 in BAT;(6)In HFD mice,single head-neck irradiation intervention significantly reduced the weight of inguinal fat and epididymal fat(Irr+HFD group vs.Ctrl+HFD group:(0.364 ± 0.035)g vs.(0.477 ± 0.033)g,P < 0.05,(0.393 ± 0.043)g vs.(0.565 ± 0.040)g,P <0.05),single head-neck irradiation intervention significantly increased the number of white fat cells per unit area(Irr+HFD group vs.Ctrl+HFD group:(52.000 ± 6.658)vs.(28.667 ±1.202),P < 0.05),however,in CD mice,single head-neck irradiation intervention had no significant effect on the weight of inguinal fat and epididymal fat and the number of white fat cells per unit area;(7)There was no significant difference in fasting blood glucose among the four groups,but in HFD mice,single head-neck irradiation intervention significantly improved the impaired glucose tolerance and significantly increased the expression of liver GLUT2(Irr+HFD group vs.Ctrl+HFD group:(1.673 ± 0.272)vs.(1.008 ± 0.097),P < 0.05),in CD mice,single head-neck irradiation intervention had no obvious effect on glucose tolerance and liver GLUT2 expression.Conclusion: In HFD mice,single head-neck irradiation intervention can increase the levels of T3 and TSH,increase the expression of BAT UCP1,promote thermogenesis,increase fat mobilization,increase the expression of liver GLUT2,and improve glucose tolerance thereby increasing the energy metabolism.However,single head-neck irradiation intervention has no obvious effects on CD mice.The above results provide a valuable reference for the clinical application of radiotherapy. |
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