Mechanism Of Omega-3 PUFA Alleviating Insulin Resistance Induced By High Fat Foods

Objective:In this study,we established a model of insulin resistance of high-fat food induced obesity in C57BL/6 mice,and explored the mechanism of omega-3polyunsaturated fatty acid??-3PUFA?on insulin resistance.Methods:C57BL/6 and FAD₃^+/-transgenic mice were fed with 10%low-fat food and45%high-fat food,40 mice were divided into 4 groups,10 in each group:10%low-fat food-fed C57BL/6 mice?C57BL6C?and FAD₃^+/-transgenic mice?FAD3C?,45%high fat diet-fed C57BL/6 mice?C57BL6H?and FAD₃^+/-transgenic mice?FAD3H?were fed for 40 weeks.During the 40 weeks,the body weight and food intake were measured every 3 days in mice.The resting metabolic rate was measured at 37 weeks,and glucose tolerance and insulin resistance were respectively measured at 38 weeks and 40 weeks.The concentrations of adiponectin,leptin and insulin were measured by ELISA;UCP1,PGC1?,PRDM16,GLUT4,SIRT1,PPAR?PPAR?,PI3K,AKT,IRS1 and IRS2 mRNA were measured by qRT-PCR;Western blot method was used to measure P38MAPK and PP38MAPK protein were by western blot.Results:The body weight of C57BL6H group was significantly higher than that of the other three groups?p<0.01?,the weight of body fat was higher than that of the other three groups?p<0.01?,and the resting metabolic rate was significantly lower than that of the other three groups?p<0.05?.There is no difference between the four groups.Glucose tolerance test and insulin resistance test showed that the glucose concentration in C57BL6H group was significantly higher than that in the other three groups at 60 min?p<0.05?.The area under the glucose curve in the C57BL6H group was significantly higher than the other three groups?p<0.05?,and the insulin concentration was significantly higher than the other three groups?p<0.01?.These data indicate that insulin resistance is induced by obesity in the C57BL6H group.Leptin was significantly higher in the C57BL6H group than in the other three groups?p<0.01?,and the adiponectin concentration was significantly higher in the FAD3H group than in the other three groups?p<0.05?.The results of mRNA in BAT?brown adipose tissue?showed that UCP1 mRNA expression was significantly higher in the FAD3H group than in the other three groups?p<0.05?,and there was no difference between the other three groups.The mRNA expression of PGC1?in C57BL6C group was lower than that in the other three groups?p<0.01?,and there was no difference between the other three groups.The expression level of PRDM16 mRNA was lower in the C57BL6C group than in the other three groups?p<0.01?,and there was no difference between the other three groups.The content of SIRT1 mRNA was significantly lower in the C57BL6H group than in the other three groups?p<0.05?,and there was no difference between the other three groups.PPAR?mRNA was significantly higher in the FAD3C group than in the other three groups?p<0.05?,and there was no difference in the other three groups.The expression of AKT mRNA in the FAD3H group was lower than that in the other three groups?p<0.05?.The expression of IRS1 mRNA was significantly lower in the C57BL6H group than in the other three groups?p<0.05?,but there was no difference between the other three groups.The expression of IRS2 mRNA was significantly higher in the FAD3H group than in the other three groups?p<0.05?.The expression of IRS2 mRNA in the C57BL6H group was the lowest?p<0.05?.There was no difference in the expression of IRS2 mRNA between the C57BL6C group and the FAD3C group.The expression of GLUT4 mRNA was higher in the FAD3C group than in the other three groups?p<0.05?.The content of GLUT4 mRNA was not different between the C57BL6H group and the FAD3H group.The expression of PI3K mRNA in C57BL6H group was significantly lower than that in the other three groups?p<0.01?.Compared with C57BL6C group,the expression of PI3K mRNA in FAD3H group and FAD3C group was significantly increased?p<0.01?,and there was no difference in expression between the two groups.The results of mRNA in WAT?white adipose tissue?showed that the expression of PGC1?mRNA was higher in the FAD3H group than in the other three groups?p<0.01?.The expression of PRDM16 mRNA in FAD3C group was higher than that in the other three groups?p<0.05?,and there was no difference in expression between the other three groups.The content of SIRT1 mRNA in C57BL6H group was lower than that in the other three groups?p<0.05?,and there was no difference in the expression of other three groups.The expression of AKT mRNA in the C57BL6C group was significantly lower than that in the other three groups?p<0.01?,and there was no difference in the expression of the other three groups.The expression of IRS1 mRNA in the FAD3C group was significantly higher than that in the other three groups?p<0.01?,and there was no difference in the expression of the other three groups.The expression of PPAR?mRNA in FAD3C group was significantly higher than that in other three groups?p<0.01?.The mRNA expression of PPAR?in C57BL6H group was significantly lower than that in other three groups?p<0.01?.Compared with FAD3H group,PPAR?mRNA in FAD3C group significantly increased expression?p<0.05?.The expression of PI3K mRNA in C57BL6H group was significantly higher than that in the other three groups?p<0.05?.Compared with C57BL6C group,the expression of PI3K mRNA in FAD3C group and FAD3H group was significantly increased?p<0.05?,and there was no difference in expression between the two groups.The expression of IRS2 mRNA in C57BL6H group was higher than that in other three groups?p<0.01?.The expression of IRS2mRNA in FAD3H group was lower than that in other three groups?p<0.05?.There was no difference in IRS2 mRNA expression between FAD3C group and C57BL6C group.Western blot analysis showed that there was no difference in expression of P38MAPK protein.The PP38MAPK of FAD3H group was significantly higher than in the other three groups?p<0.01?.Conclusion:Endogenous Omega-3 PUFA reduced the weight gain in induced by high-fat foods.High-fat food-induced insulin resistance was attenuated by regulating fat hormone levels and expression of adipose differentiation factors and insulin receptor substances and PI3K and P38MAPK.