β-hydroxy-β-methylbutyrate Improves Chronic Renal Failure-Induced Sarcopenia in SD Rats by Regulating Autophagy

Background Chronic renal failure-induced sarcopenia (CRF-S) seriously affects public health by increasing morbidity and mortality. This study evaluated the therapeutic effects of β-hydroxy-β-methylbutyrate acid (HMB) and the underlying mechanism in an adenine-induced CRF-S rat model. Methods Sprague Dawley rats were divided into control, model (CRF-S), and HMB treatment (CRF-S+HMB) groups. The rats in the CRF-S group received 250 mg/kg/d adenine by oral gavage every day for 14 days, followed by administration every other day until the 28th day. In the CRF-S+HMB group, each rat was given 320 mg/kg/d HMB by oral gavage starting from 7 days prior to adenine treatment, and this treatment was maintained for a total of 35 days. The body weight, right anterior tibial muscle weight, blood serum parameters, gastrocnemius muscle and renal tissue histology, and expression of autophagyrelated transcripts and proteins were evaluated. Results A rat model of CRF-S was successfully established via adenine gavage, as indicated by reduced body weight and muscle weights, and markers of sarcopenia. There were increased mRNA levels of LC3B, Beclin1, Ulk1, Atg5, Atg7, Atg13 and vps-34, and increased protein expression levels of LC3B and P62. In the rats with HMB intervention, the body weight, right anterior tibial weight and gastrocnemius muscle histology were not signifcantly different from those in the control group, and the expression levels of autophagy-related proteins (LC3B and P62) were consistent with those in the control group. Conclusion We successfully established a rat model of CRF-S using adenine administered via oral gavage, and observed that HMB treatment prevented CRF-S, apparently by regulating autophagy. HMB may be an effective agent for the prevention and treatment of CRF-S.