| Purpose: High-fat diets and sedentary lifestyles are the main causes of the high incidence of many chronic diseases today.Long-term regular exercise as a healthy and effective means of preventing and delaying the onset of chronic diseases.Studies have shown that skeletal muscle is the main organ that performs exercise,and micro RNA-206(miR-206),a skeletal muscle-specific miRNA,which plays an important role in regulating body fat metabolism and the changes in skeletal muscle caused by exercise.Histone deacetylase 4(HDAC4),a transcriptional repressor,also has important effects on body lipid metabolism,while miR-206 can inhibit HDAC4 protein expression in skeletal muscle cells and regulate glucose metabolism.Therefore,we hypothesized that aerobic exercise might improve skeletal muscle lipid metabolism by regulating miR-206 levels and thus HDAC4 protein expression.In this paper,high-fat diet and aerobic exercise intervention methods are used to observe the changes of mouse body weight and blood lipid indexes,to study the effects of aerobic exercise on lipid deposition,miR-206,HDAC4 and lipid metabolism-related proteins in mouse skeletal muscle,and to explore miR-206's role in aerobic exercise in regulating lipid metabolism.METHODS: Forty 4-week-old male C57BL/6J mice were selected for this study,randomly divided into normal diet and high-fat diet groups,housed for 8 weeks,and then randomly divided into 4 groups: normal quiet group(NC),normal exercise group(NE),high-fat quiet group(HC)and high-fat exercise group(HE),10 mice in each group.The mice in the exercise group were trained with aerobic running platform exercise at 75% VO2 max for 60 min per day,5 days per week for 6 weeks.The mice were weighed weekly during exercise,and at the end of exercise,the mice were executed and samples were taken.Serum was extracted and serum triglyceride(TG)and free fatty acid(FFA)levels were measured by ELISA;mouse flounder muscle was isolated and stained with Oil Red O to detect lipid deposition in mouse flounder muscle;miR-206 levels in mouse flounder muscle were measured by Real-time PCR;Western blot detection of HDAC4,fatty acid synthase(FAS),acetyl coenzyme A carboxylase(ACC),phosphorylation of acetyl coenzyme A carboxylase(p-ACC)and carnitine palmitoyl transferase 1b(CPT1b)protein expression in mouse flounder muscle.Results:(1)Compared with the NC group,the mice in the HC group showed a significant increase in body weight,serum TG and FFA levels(P<0.01)and a significant increase in skeletal muscle lipid deposition(P<0.01);compared with the HC group,the mice in the HE group showed a significant decrease in body weight,serum TG and FFA levels(P<0.05)and a significant improvement in skeletal muscle lipid deposition(P<0.01).It is suggested that aerobic exercise can significantly reduce body weight,blood lipid level and skeletal muscle lipid deposition in mice on high-fat diet.(2)Compared with the NC group,the skeletal muscle miR-206 level was significantly higher in the NE group(P<0.01);compared with the HC group,the skeletal muscle miR-206 level was significantly higher in the HE group(P<0.01).(3)Compared with the NC group,the protein expression of HDAC4 and CPT1b in skeletal muscle was significantly lower in the NE group(P<0.05),while the protein levels of HDAC4,FAS and ACC in skeletal muscle were significantly increased in the HC group(P<0.05)and the protein expression of p-ACC and CPT1b was significantly lower in the HE group(P<0.05);compared with the HC group,the protein expression of HDAC4,FAS and ACC in skeletal muscle was significantly lower in the HE group(P<0.05).The protein expression of HDAC4,FAS and ACC in skeletal muscle was significantly lower(P<0.05)and that of p-ACC and CPT1b was significantly higher(P<0.05)in the HE group compared with the HC group.Conclusion:Aerobic exercise may ameliorate the abnormal skeletal muscle lipid metabolism induced by high-fat diet in mice by up-regulating the level of miR-206 in mouse skeletal muscle and thus inhibiting the protein expression of HDAC4. |
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