Effect Of Aerobic Exercise Combined With Glycyrrhizic Acid On Lipid Metabolism In Skeletal Muscle Of T2DM Rats

Objective: Insulin resistance is the main characteristic of type 2 diabetes mellitus(T2DM),accompanied by decreased or relative decrease of insulin secretion caused by functional impairment of pancreatic β cells,and the body’s ability to regulate glucose metabolism is decreased.AMP-activated protein kinase(AMPK)is a regulator that maintains intracellular energy balance and regulates various metabolism-related hormones.Phosphatidy inositol3-Kinase(PPAR)is an important transcription factor regulating adipocyte differentiation.AMPK/PPARγ is closely related to the glycolipid metabolic pathway of T2 DM.AMPK/PPARγ can effectively mobilize the regulating ability of lipid metabolism by increasing the expression of AMPK/ Pparγ,reduce the level of blood lipid and IR of various tissues and organs,and play a significant role in improving the disorder of lipid metabolism.Skeletal muscle is an important organ for IR expression and is one of the most active parts of fatty acid oxidation metabolism,which is closely related to lipid metabolism regulation of T2 DM.Studies have shown that regular exercise can increase the insulin sensitivity of peripheral tissue cells,improve body composition,help control blood sugar,and have a significant effect on the prevention and improvement of diabetes.Glycyrrhizic acid has the effects of anti-steatosis,anti-oxidation,improving glycolipid metabolism and liver protection,and can also regulate the disorder of glycolipid metabolism in the body.At present,existing studies have focused on the effect of exercise and glycyrrhizin alone on T2 DM,while the effect of combined therapy of exercise and glycyrrhizin on skeletal muscle lipid metabolism.Therefore,in this study,8-week aerobic exercise combined with glycyrrhizic acid was used to intervene in T2 DM rats,to explore the effect of aerobic exercise combined with glycyrrhizic acid intervention on skeletal muscle lipid metabolism of T2 DM rats,as well as the mechanism of AMPK/PPARγ signaling pathway in the regulation of lipid metabolism of T2 DM,providing certain theoretical and experimental basis for the treatment of T2 DM.ResearchMethods: Thirty 4-week-old male SD rats were randomly divided into normal control group(NC group),DM model group(DM group),glycyrrhizin drug group(GA group),moderate exercise group(MIT group)and glycyrrhizin + moderate exercise group(GM group).The NC group was fed ordinary maintenance diet all the time.After the other four groups were fed high-fat and high-sugar diets for 8 weeks,streptomycin was injected into the rats’ body weight.After successful modeling,GA group and GM group were given 200mg/kg glycyrrhizic acid by gavage for 8 weeks,and MIT group and GM group were given treadmill exercise for 8 weeks.After the intervention,the samples were taken under anesthesia,the serum of rats was used for blood glucose,blood lipid and serum insulin,the gastrocnemius muscle was taken for HE staining to observe the structural changes of the skeletal muscle of rats,and the supernatant of gastrocnemius muscle was taken by homogenate centrifugation for TC and TG content detection to observe the changes of lipid metabolism indexes of the skeletal muscle of rats.The expressions of AMPK and PPARγ in skeletal muscle were detected by Western Blot.Results: 1)The results of body weight showed that after 8 weeks of high fat and high sugar feeding,compared with NC group,the weight growth rate of rats in DM group,GA group,MIT group and GM group was higher than that in NC group,with a significant difference(P < 0.05).The body weight of T2 DM rats showed a continuous trend of forehead decline after the intervention,compared with DM group,After exercise and GA intervention,the weight loss rate of rats in GA group,MIT group and GA group was significantly slower with a slow recovery trend(P < 0.05).2)Blood glucose and serum insulin indexes showed that compared with NC group,blood glucose level and serum insulin level of T2 DM rats in four groups were significantly increased(P < 0.05),insulin resistance index was significantly higher than NC group(P < 0.01),after 8 weeks of exercise and GA intervention,The levels of blood glucose and IR in GA,MIT and GM groups were significantly decreased compared with those in DM group(P < 0.01).3)Blood lipid level results showed that compared with the NC group,the levels of TC,TG,LDL and HDL of the four groups of T2 DM rats were significantly increased,and lipid metabolism disorder was obvious.After 8 weeks of exercise and GA intervention,the blood lipid levels of the GA group,MIT group and GM group were reduced to varying degrees,among which,compared with the DM group,The decrease of TC level in GA group had significant difference(P < 0.05),while the decrease of TG,LDL and HDL had no significant difference(P > 0.05);the decrease of TC and TG level in MIT group had significant difference(P < 0.05),but the decrease of LDL and HDL had no significant difference(P > 0.05).There were significant differences in TC,TG,LDL and HDL levels in GM group(P < 0.05).4)TC and TG contents in skeletal muscle showed that compared with NC group,TC and TG contents in skeletal muscle of rats in four groups with significant differences(P <0.05),and obvious lipid deposition was observed in skeletal muscle.Compared with DM group,TC content in GA group,MIT group and GM group was decreased,with significant difference(P < 0.01),TG content in GM group was significantly decreased,with significant difference(P < 0.05),TG content in GA group and MIT group was not significantly decreased,with no significant difference(P > 0.05).5)The results of HE staining showed that the skeletal muscle cells in NC group were evenly arranged,the intercellular space was clearly demarcated,and the cell morphology was normal and the structure was complete.Compared with the NC group,the skeletal muscle connective tissue of the DM group was increased,the cell space was significantly enlarged,and more serious inflammatory infiltration appeared.Compared with the DM group,the skeletal muscle fine connective tissue of the GM group was relatively less,the cell space was reduced,the inflammatory infiltration was lighter,and the tissue morphology was significantly improved.6)Western Blot showed that compared with NC group,the expression of AMPK/PPARγ protein in DM group was significantly decreased(P < 0.05).Compared with DM group,the relative expression of AMPK protein in GA group,MIT group and GM group was significantly increased(P < 0.01),with GM group > MIT group > GA group.Compared with the DM group,the relative expression of PPARγ protein in the MIT group and the GM group was significantly increased(P < 0.05),the GM group was > MIT group,and the GA group was not significantly increased(P > 0.05).Conclusions:1)After 8 weeks of aerobic exercise and glycyrrhizic acid intervention,hyperglycemia,hyperlipidemia and insulin resistance of T2 DM rats were improved to some extent.2)Aerobic exercise,glycyrrhizic acid and exercise-combined glycyrrhizic acid intervention all improved the lipid metabolism disorder of T2 DM rats to varying degrees,among which exercise-combined glycyrrhizic acid intervention had the most obvious effect,followed by aerobic exercise and glycyrrhizic acid intervention.3)After 8 weeks of aerobic exercise combined with glycyrrhizic acid intervention,TC and TG contents in skeletal muscle of T2 DM rats were effectively reduced,and protein expressions of AMPK and PPARγ were increased.The mechanism may be that AMPK/PPARγ protein expression,which is closely related to lipid metabolism in skeletal muscle,was up-regulated,thereby alleviating lipid deposition and lipid metabolism disorder,and improving insulin resistance.