| With the development of modern society, various diseases have been successfully eliminated, which greatly improves the life quality of human beings. However, at the meantime, high-fat diet and lack of exercise have caused increased incidence of metabolic diseases, such as obesity and diabetes, both of which are usually accompanied with insulin resistance. Bruce M. Spiegelman from Harvard Medical School firstly brought up the notion that inflammation is the real cause of insulin resistance. Inflammation has been listed as the theme of 2014 ACSM annual meeting due to the more and more attention paid to its effect on exercise, health and diseases. Obesity and diabetes are usually accompanied with chronic inflammation, with the increase of pro-inflammatory factors, such as TNF-a, interleukin-1β (IL-1β), transforming growth factor (TGF-β) and monocyte chemotactic protein-1 (MCP-1/CCL2), as well as decrease of anti-inflammatory factors, such as IL-10. Therefore, investigation of the underlying mechanism of inflammatory regulation is essential to exploring insulin resistance. Until recently, Jun N-terminal kinase (JNK), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in the adipose tissue and liver have been the main focus of researches of this field. However, evidence suggested that skeletal muscle was also the key site of formation and accumulation of chronic inflammation, and that AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homologl (SIRT1)/NF-κB might be involved in some way. To author’s knowledge, there have been few studies regarding the effect of exercise on inflammatory response via AMPK/SIRT1/NF-κB pathway. Therefore, the purpose of the present study was to investigate the effect of exercise on inflammation in the skeletal muscle of diabetic mice as well as its underlying mechanism, with the hope of providing theoretic evidence for prevention and treatment of obesity and diabetes.Purpose:The purpose of the present study was to investigate the effect of endurance exercise on inflammatory factors and corresponding signaling pathways in the skeletal muscle, as well as to explore tentative mechanism by establishment of diabetic mice model and interference with 6-week swimming, hoping to provide new evidence for the prevention and treatment of obesity and diabetes from the perspective of inflammation of the skeletal muscle.Methods:39 clean grade male C57BL/6 mice of 4-week old, with body weight of 16.49 ±1.50g were used.16 mice were randomly chosen and assigned to either control group (C, n=8) or exercise group (E, n=8), and were fed with standard chow. The rest 23 mice were fed with high-fat diet for 4 weeks, and then injected with Streptozotocin for five days. Mice with fasting glucose level higher than 9mmol/L were considered as diabetic mice.16 diabetic mice were randomly chosen and assigned to either diabetic group (D, n=8) or diabetic exercise group (DE, n=8), and were fed with standard chow. Groups E and DE were then interfered with 6-week swimming exercise of moderate intensity, one hour per day, five days per week. RT-PCR was used to measure the mRNA expression of TNF-a, CCL2, IL-6, IL-10, AMPKα1, AMPKα2, SIRT1 and NF-κBp65. Western Blotting was used to measure the protein level of AMPK, p-AMPK, SIRT1, NF-κcBp65 and AC-NF-κBp65Results:1)Compared with group C, the weight of mice in group E decreased significantly(P<0.05), meanwhile, the weight of mice in group D also decreased significantly(P<0.01); While the weight of mice in DE group didn’t change when comparing with group D,The weight of mice in group DE decreased significantly when compared with group E.2) Compared with group C, the fasting bloodglucose in group E mice didn’t change,while the fasting blood glucose in group D increased significantly (P<0.01);Compared with group D, the the fasting blood glucose in group DE decreased significantly(P<0.05).3) Compared with group C, the IL-6 mRNA expression in group E was increased significantly(P<0.05), the IL-10 mRNA expression in group E was also increased significantly(P<0.01);Compared with group C.the IL-10 mRNA expression in group D was decreased significantly(F<0.01);Compared with group D, the TNF-a mRNA in group DE was decreased significantly(P<0.05), the IL-10 mRNA in group DE was increased significantly(P<0.01); Compared with group E,the IL-6 mRNA of group DE was decreased significantly(P<0.05).4)Compared with group C, the gene expreesion and activity of AMPK^ SIRT1、NF-κBp65 didn’t change significantly; Compared with group C, the protein expression and activity of AMPK were decreased significantly(P<0.05) in group D, while the mRNA of NF-κBp65 was increased significantly(P<0.01) in group D; Compared with group D, the mRNA of AMPKa2 and SIRT1 were increased significantly(P<0.01) in group DE,the protein expression of AMPK、p-AMPK and the activity of AMPK were increased significatly(P<0.05), while the protein expression of NF-κBp65 was decreased significantly (P<0.01); Compared with group E, the mRNA of SIRT1 increased significantly(P＜0.01).Conclusions:1) The weight of diabetic mice decreased significantly, and the fasting blood-glucose increased significantly.6 weeks of swimming have no effect on weight, however, the fasting blood-glucose decreased significantly.2) The mRNA expression of anti-inflammatory factor IL-10 in skeletal muscles of the diabetic mice decreased significantly.6weeks of swimming decreased the mRNA expression of pro-inflammatory factor TNF-α,but mRNA expression of IL-10 increased significantly. It means that the inflammatory factors may take part in the anti-inflammtion effect by exercise.3) The protein expression and activity of AMPK in skeletal muscles of diabetic mice decreased significantly, but the expression of SIRT1 and the acetylation of NF-κB didn’t change, the mRNA of NF-icBp65 increased significantly.It means that the suppression of AMPK leads to the elevation of NF-κB and the IL-10 mRNA.6 weeks of swimming can increased the expression and activity of AMPK, SIRT1 mRNA significantly. But the protein expression of NF-κBp65 decreased significantly, the mRNA of TNF-a decreased and IL-10 increased significantly. It means that exercise can reverse relieve the suppression of AMPK/SIRT1/NF-κB by diabetes. |
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