| Objective:(1)To establish mouse model with four different Lee’s index:Thin,WT(wide type),OW(overweight),and Ob(obesity);(2)To investigate the effects of head and neck radiation on the content of triglycerides and free fatty acids in the plasma of mice with different Lee’s index;(3)To investigate the effect of head and neck radiation on the expression of appetite-promoting neuropeptide agouti-associated protein in the paraventricular nucleus of mice with different Lee’s index;(4)To investigate the effects of head and neck radiation on glucose metabolism in mice with different Lee’s index;(5)To investigate the effects of head and neck radiation on lipid metabolism in mice with different Lee’s index.Methods:(1)4-week-old male C57BL/6 mice were randomly divided into four groups after one week of normal diet acclimatization,and the following methods were used:the Thin group was fed with a normal diet but with restricted dietary time and an eight-hour diet(eating from 10 pm to 6 am);the WT group was fed with a normal diet with free eating time;the OW group was fed with a high-fat diet(D12492)with an eight-hour diet(eating from 10 pm to 6 am);the Ob group was fed with a high-fat diet(D12492)with free eating time.(2)After successful modeling,at 9 am on the 43rd day,we selected a certain number of mice from each of the four groups for disposable 6Gy(Its photon energy is 6MV,and its dose rate is 2.3Gy/min)head and neck radiation.(3)The levels of plasma triglycerides(TG)and free fatty acids(FFA)were detected by enzyme-linked immunosorbent assay(ELISA).(4)The effect of head and neck radiation on the expression of AgRP in the hypothalamic PVN nuclei of mice with different Lee’s index was detected by immunofluorescence technology.(5)Glucose metabolism-related detection:fasting blood glucose was measured by tail vein blood collection,and IPGTT was injected to evaluate the glucose tolerance of mice.(6)Lipid metabolism-related detection:the number of lipid droplets in liver tissue was observed by oil red O staining experiment;the number of cells in brown adipose tissue(BAT)and white adipose tissue(WAT)was counted by Hematoxylin-eosin staining(HE)staining;the expression of UCP1 in brown fat and white fat was detected by western blot.Results:1.Modeling of mice with four different Lee’s index:(1)Lee’s index(3(?)((body weight g*1000)/length cm)):Control group(13.72 ± 0.25),Thin group(13.45 ±0.35),OW group(13.99 ± 0.17),Ob group(14.26 ± 0.12).(2)Weight(g):control group(23.93 ± 1.37),Thin group(22.25 ± 2.11),OW group(24.60 ± 1.39),and Ob group(26.49 ± 0.69).2.Head and neck radiation increased the plasma triglyceride content of mice in the Thin group and the Ob group:(1)After head and neck radiation intervention,TG(ng/L)levels were elevated in the Thin(P<0.01)and Ob(P<0.05)groups compared with the control group receiving radiation,and there was no significant difference in the IR-OW group(P>0.05).(2)FFA(umol/L)levels were relatively elevated in four groups following head and neck radiation intervention.3.Expression of AgRP in PVN in hypothalamus:the expression of AgRP was higher in the PVN in IR-Ob group,(P<0.05),compared with IR-WT group.While the IR-Thin and IR-OW groups were not statistically different from them(P>0.05).4.Regarding glucose metabolism,head and neck radiation increased fasting blood glucose in mice in the Thin and Ob groups and caused changes in food intake:(1)Compared with control mice receiving radiation intervention(IR-WT),head and neck radiation increased fasting blood glucose(mmol/L)in the IR-Ob group(P<0.05).At the same time,there was no significant difference in the IR-OW group.(2)Compared with the control mice receiving radiation intervention(IR-WT),the head and neck radiation intervention reduced the mass(g)of cumulative nocturnal food intake in the IR-Thin,IR-OW,and IR-Ob groups.5.Regarding lipid metabolism,head and neck radiation increased liver lipid droplets in mice in the Ob group,decreased the number of white adipocytes per unit area in the Thin group,and decreased the expression of UCP1 in brown fat and white fat in the four groups:(1)Liver oil red O:lipid droplets were more in the liver of the IR-Ob group receiving radiation relative to the control and IR-OW groups(P<0.05).(2)Effect of head and neck radiation on brown adipose tissue:after head and neck radiation intervention,UCP1 expression was higher in the IR-OW and IR-Ob groups compared with the IR-WT group(P<0.05).Relative to the paired-fed un-radiated group,all four groups that received radiation showed a trend of decreased UCP1 expression,but it was not statistically significant(P>0.05).(3)Effect of head and neck radiation on white adipose tissue:compared with the IR-WT group,head and neck radiation caused a decrease in the number of cells and an increase in cell volume per unit area in the IR-Thin group(P<0.05);there was no statistical difference between the IR-OW and IR-Ob groups(P>0.05).There was no statistical difference in UCP1 expression between the four groups after the head and neck radiation intervention(P>0.05).However,among the groups that did not receive radiation,the UCP1 expression in the Ctrl-OW group was highest(P<0.05).Conclusions:This study showed that the changes in energy metabolism caused by ionizing radiation in mice with various Lee’s index are different.After being stimulated by ionizing radiation,relative to the control group of mice,fasting blood glucose was increased,and glucose tolerance was impaired in obese and thin mice.Still,these changes did not occur in mice of the IR-OW group.Ionizing radiation increased triglyceride levels in the plasma of the IR-Ob group and IR-Thin group of mice and increased lipid droplets in the liver of the IR-Ob group of mice.The expression of UCP1 in white adipose tissue was increased in mice without ionizing radiation,promoting browning and improving body metabolism.In conclusion,it is hypothesized that the body with a little more fat content can resist the hazards of ionizing radiation by enhancing the metabolic balance of UCP1. |
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