Effects Of Swimming On Liver Fat Deposition And Insulin Resistance In Type 2 Diabetic Mice

Object:At present,about 1 in 11 adults in the country has diabetes,90% of whom have type 2 diabetes(T2DM),and Asia is the center of the global T2 DM epidemic.The main drivers of T2 DM epidemic include obesity,sedentary,poor lifestyle and increased calorie intake.Ectopic fat deposition is one of the strongest predictors of T2 DM and is closely related to insulin resistance.The mechanism of swimming regulating liver fat deposition has not been elucidated.Therefore,in this study,the mouse model of type 2 diabetes was established and swimming intervention was carried out to explore the improvement mechanism of swimming on liver fat deposition by detecting the expression of insulin signal pathway genes,fat deposition related genes,inflammatory factors and oxidative stress related genes in liver,so as to provide a theoretical basis for swimming to improve T2 DM.Methods:Four-week-old C57BL/6J male mice were randomly divided into control group(con,n=8,normal diet)and high-fat diet-induced group(HFD,n=20,high-fat diet).Type 2 diabetes model was induced by intraperitoneal injection of STZ after 12 weeks of high-fat diet.The establishment of the mouse model was evaluated by measuring body weight,fasting blood glucose,glucose tolerance(GTT)and insulin tolerance(ITT)test.The successfully established mice were randomly divided into diabetic quiet group(SED,n=8,high fat diet)and swimming group(SW,n=8,high fat diet).The SW group received swimming training for 8 weeks,5 days a week,1 hour a day.After 8 weeks of swimming intervention,the liver tissue was sliced and stained with HE and Oil Red O to observe the effect of exercise on liver fat deposition.Total liver RNA was extracted and RT-PCR,was used to detect the expression of main factors of insulin signaling pathway(IRS,PI3 K,AKT),liver fat deposition related factors(FATP1,CD36,ACC1,SCD1,APOB100,PPAR-?,CPT-1,FXR),inflammatory factors(CD86,iNOS,IL-6,IL-1 ?,TNF-?,Arg),oxidative stress related genes(NOX2,PRDX1).Results: 1.Establishment of diabetes model.After 12 weeks of high fat feeding,the body weight and fasting blood glucose of HFD group were higher than those of con group(P<0.05).The area under the curve of GTT and ITT showed that the area of HFD group was significantly larger than that of con group(P<0.05).The results showed that the model of type 2 diabetes was established successfully.2.Effects of swimming on body weight and fasting blood glucose in mice.After 8 weeks of exercise,the body weight of mice in the SW group was significantly lower than that in the SED group,and was close to that in the con group.The abdominal fat rate of SED group was significantly lower than that of SED group(P<0.05).Although the fasting blood glucose did not return to normal,the blood glucose of SW group was significantly lower than that of SED group(P<0.05).Although the fasting blood glucose of SW group did not return to normal,the abdominal fat rate of SW group was significantly lower than that of SW group(P<0.05).The results showed that swimming for 8 weeks could reduce the body weight and abdominal fat rate of mice.3.Effects of swimming on glucose tolerance and insulin tolerance in mice.The area under GTT curve in SED group and SW group was significantly larger than that in con group.The area under ITT curve in SED group and SW group was significantly larger than that in con group,but that in SW group was significantly lower than that in SED group(P<0.05).The results showed that 8-week swimming exercise had a tendency to improve the insulin sensitivity of mice.4.Effect of swimming on insulin pathway in mice.The results showed that the expression of IRS,PI3 K and AKT mRNA in SED group was significantly lower than that in),SW group,but after 8 weeks of swimming,the expression of IRS,PI3 K and AKT mRNA in SW group was significantly higher than that in SED group(P<0.05).The results showed that 8-week swimming improved insulin resistance in mice.5.Effect of swimming on fat deposition in liver of mice.The results showed that the liver weight of SED group increased significantly,about 2 times,and there was no significant difference in SW group,but after 8 weeks of swimming,the liver weight of SW group was significantly lower than that of SED group,and close to that of con group.HE staining showed that there were a large number of fat vacuoles in SED group,a lot of red lipids were stained in SED group,and a small amount of fat vacuoles and red lipids were found in SW group.The content of TG in liver of SED group was significantly higher than that of SED group(P<0.05).In SW group there was no significant difference,but the content of TG in liver of SW group was significantly lower than that of SED group(P<0.05).In SED group,the expression of FATP1,CD36,ACC1,SCD1 and APOB100 mRNA increased significantly,while the expression of PPAR-?,CPT-1 and FXR mRNA decreased significantly(P<0.05).In SW group that the expression of FATP1,CD36,ACC1,SCD1 and APOB100 mRNA decreased significantly,while the expression of PPAR-?,CPT-1 and FXR mRNA increased significantly.The results showed that 8-week swimming improved fat deposition in the liver of mice.6.Effect of swimming on inflammatory factors in the liver of mice.M1 macrophages were labeled with iNOS and total macrophages were labeled with Mac-2.Immunofluorescence results showed that M1 macrophages were significantly increased in SED group and less in SW group.The expression of CD86,iNOS,IL-6,IL-1 ? and TNF-? mRNA was significantly increased in SED group(P<0.05).In SW group that Arg mRNA expression was significantly decreased(P<0.05).The expression of iNOS,IL-6 and IL-1 ? mRNA was significantly decreased in),SW group(P<0.05).The results showed that 8-week swimming improved the inflammatory response in mice.7.Effect of swimming on oxidative stress in the liver of mice.In SED group,the expression of oxidative stress factor NOX2 mRNA was significantly increased,while the expression of antioxidant stress factor PRDX1 mRNA was significantly decreased(P<0.05).In SW group that expression of NOX2 mRNA was significantly decreased,and the expression of PRDX1 mRNA was significantly increased(P<0.05).The results showed that 8-week swimming improved oxidative stress in mice.Conclusion:Swimming can improve insulin resistance and insulin sensitivity in T2 DM mice,which may be related to the improvement of liver function.Swimming can reduce liver weight,improve liver fat deposition,reduce liver inflammation and oxidative stress in T2 DM mice.The mechanism of swimming to improve the fatty deposition of liver may be related to the inhibition of fatty acid intake protein(FATP1)and adipogenesis factor(ACC1,SCD1).Promoting the expression of PPAR-?,CPT1 and FXR are related.