| Background: The world is aging today,and the incidence rate of chronic diseases in the elderly always be higher.Although all the molecular mechanisms related to agerelated diseases are not clearly,low-grade chronic inflammation seems to be highly correlated.Obesity and sarcopenia(OBSP)is often accompanied by aging,and Innate immunity and NLRP3 inflammasome play a key role in maintaining this chronic inflammatory state,it is shown that NLRP3 has the ability to participate in many dangerous signals which associated with aging and can further promote the immune response.Therefore,NLRP3 inflammasome seems to be not only a therapeutic target for OBSP,but also for the whole aging process.Aging declined protein synthesis,but exercise can increase skeletal muscle protein synthesis,improve quality and strength of muscle,the specific mechanism remains to be clear.However,whether exercise can regulate inflammatory response,promote muscle protein synthesis,improve skeletal muscle fat deposition and muscle attenuation by inhibiting NF-κB/NLRP3 remains to be further studied.Objective: To start with NLRP3 signaling pathway to study the effects of resistance and aerobic exercise on muscle strength and quality in aging mice,to explore the molecular mechanism of the MSTN/PPARγ/NF-κB /NLRP3 signaling pathway,which leads to muscle fat liquid accumulation and muscle atrophy。It also provides more kinds of sight about exercise intervention to prevent skeletal muscle atrophy and chronic inflammatory。Method: 25 BALB/C healthy male mice were divided into four groups randomly: quiet normal diet control group,quiet high-fat diet control group,high-fat diet resistance treadmill training group,high-fat diet resistance training group.The weight and grip strength of all mice were measured every week,and the maximum load of each mouse in the resistance training was tested as the basis for next week’s training.After the experiment,the mice were killed and the quadriceps femoris was removed quickly.The protein expression of NLRP3,NF-κB,MSTN,IL-1β,TNF-α and the protein expression of PI3 K,sirt2,PPARγ in quadriceps femoris were detected by Wes;the condition of adipocytes from liver and i WAT were detected by oil red staining.SPSS software was used to analyze the data by one-way ANOVA and paired sample t-test.Result:(1)The change of body weight and muscle wet weight: the movement of mice(R-HFD group and R+A-HFD)weight in eight weeks there is always higher than the exercise group(C-HFD group and C group),group exercise mice,the weight increased and small first,not exercise group always losing weight,but no significant difference and the four groups of the first week and 8 week weight had no significant difference in each group.(2)Changes in grip strength: the grip strength of the four groups decreased gradually.At the second week,the grip strength of the R-HFD group and the R+A-HFD group were significantly higher than that of the C-HFD group(P<0.05);At week 8,grip strength in the R+A-HFD group was significantly higher than that in the C-HFD group(P<0.05)(3)Expression of genes related to TNF-α/MSTN/PPARγ/NF-κB/NLRP3/IL-1βsignaling pathway: Compared with C-HFD group,TNF-α protein expression in the quadriceps femoris of mice in R-HFD group and R+A-HFD group was significantly decreased(P < 0.01).The expression of TNF-α protein in R-HFD group was significantly lower than that in C group(P<0.05),R+ A-HFD group was significantly lower than C group(P<0.01).Compared with C group and C-HFD group,the protein expression of MSTN in the quadriceps femoris of mice in R+A-HFD group was significantly decreased(P<0.05).Compared with C-HFD group,the expression of PPARγ protein in R-HFD group,R+A-HFD group and C group was significantly upregulated(P<0.01).Compared with C-HFD group,the protein expression of NF-κB in the quadriceps femoral muscle of mice in R-HFD group and R+A-HFD group was significantly decreased(P < 0.01);Compared with C group,C-HFD group was significantly up-regulated(P<0.05).The R+A-HFD group was significantly lower than the C group(P<0.05).Compared with the other groups,the protein expression of NLRP3 in the quadriceps femoris of C-HFD group was significantly up-regulated(P<0.05).Compared with C-HFD group,the protein expression of IL-1β in the quadriceps femoris of mice in R-HFD and R+A-HFD groups was significantly decreased(P<0.01).IL-1β protein expression in R+A-HFD group was significantly decreased compared with that in C group(P<0.05),significantly decreased in R-HFD group compared with C group(P<0.01).(4)Expression of genes related to PI3K/AKT/ FOXO1 /NF-κB/NLRP3 signaling pathway: Compared with C-HFD group and C group,the protein expression of PI3 K in the quadriceps femoris of mice in R-HFD group was significantly up-regulated(P<0.01);Compared with C-HFD and C groups,the R+A-HFD group was significantly upregulated(P<0.05).Compared with R+ A-HFD group,PI3 K protein expression was significantly up-regulated in R-HFD group(P<0.05).Compared with C-HFD group and C group,the expression of FOXO1 protein in the quadriceps femoris of R+A-HFD group and R-HFD group was significantly decreased(P<0.05).Conclusion(1)The combination of 8 weeks of resistance exercise and resistance running platform exercise can effectively reduce the body weight of aging mice on high fat diet,and the combination of resistance running platform exercise can significantly slow down the decline of muscle strength of aging mice on high fat diet compared with single resistance exercise.(2)Eight weeks of resistance exercise and anti-resistance running platform combined exercise can increase the protein synthesis level of high fat diet aging mice through PI3K/ AKT/FOXO1 /NF-κB/NLRP3 signaling pathway,down-regulate the expression of FOXO1 and NF-κB,and the effect of resistance exercise is better than that of antiresistance running platform combined exercise.(3)Eight-week anti-resistance exercise and anti-resistance running platform combined exercise can reduce lipid droplets and inflammatory response in skeletal muscle of aging mice with high fat diet by inhibiting TNF-α /MSTN /PPARγ / NF-κB /NLRP3 signaling pathway,thus delaying the generation of obesity sarcopenia. |
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