β-HYDROXY-β-METHYLBUTYRATE PROMOTES PROTEIN SYNTHESIS OF THE OVERLOADED SKELETAL MUSCLE IN OVARIECTOMIZED MICE
Objective To investigate the effect of β-hydroxy-β-methylbutyrate(HMB)supplementation on compensatory hypertrophy of skeletal muscle in ovariectomized mice and its possible mechanism.Methods Sixteen adult female C57 mice were subjected to ovarian removal surgery.After a week,they were treated with distal tenotomy of gastrocnemius muscle in the right hind limb,resulting in overloaded skeletal muscle hypertrophy(overload,Ovld side),and the other side underwent the sham surgery(Sham side).They were randomly divided into control group(n=8)and HMB supplementation group(n=8).HMB was supplemented by intragastric administration(0.5 g/kg)once a day.The control group was given the same amount of normal saline.The experiment lasted for 7d.Before and after the intervention,the body weight was recorded and the body composition was measured by Echo MRI.The mice were intraperitoneally injected with puromycin(0.04 μmol(/g.bw))18h before extraction.The plantaris muscle was taken and weighed.The protein expression of mTOR,S6,Akt and their phosphorylation levels and protein synthesis rate were measured by western blotting.Results After the intervention,compared with the Sham side,the muscle mass of plantaris in the Ovld side increased significantly(P<0.01).The relative expression of p-mTOR/mTOR,p-S6/S6 and p-Akt/Akt in the plantaris muscle of Ovld side increased,and p-mTOR/mTOR and p-S6/S6 increased significantly in the HMB group(P<0.05).The protein synthesis rate of the plantaris muscle in the Ovld side was increased,with a significant increase in the HMB group(P<0.05).Compared with the control group,the muscle mass of plantaris on both sides was significantly increased in the HMB group(P<0.01),and the body fat percentage reduced without a significant difference(P>0.05).The ratios of p-mTOR/mTOR,p-S6/S6 and p-Akt/Akt of the ipsilateral muscle were increased in the HMB group,but only the p-mTOR/mTOR and p-S6/S6 ratios had a significant difference(P<0.05).The protein synthesis rate in the HMB group was significantly increased(P<0.05).Conclusion HMB promotes skeletal muscle hypertrophy and increases protein synthesis in mice with distal gastrocnemius tenotomy by regulating protein synthesis signals mTOR and S6.[ACTA NUTRIMENTA SINICA,2024,46(4):334-339]