Abstract
BACKGROUND: β-hydroxy-β-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that promotes muscle protein synthesis and inhibits muscle cell degradation. This study aimed to clarify the effects of HMB on skeletal muscle mass loss using a mouse model of esophageal squamous cell carcinoma (ESCC). METHODS: ESCC cells (TE-8) (5×10(6) cells/body) were subcutaneously transplanted into 10 nude mice to generate a mouse model of ESCC. Thirteen mice were divided into three groups: (I) non-tumor group (n=3), non-ESCC mice fed a normal diet; (II) ESCC + HMB group (n=5), ESCC-bearing mice fed HMB; (III) ESCC control group (n=5), ESCC-bearing mice fed a normal diet. A powdered Ca-HMB product was used as the HMB source. Body weight, grip strength, and gastrocnemius muscle weight of the three groups of mice were measured and compared. RESULTS: Body weight did not differ between the ESCC + HMB and ESCC control groups. Grip strength and gastrocnemius muscle weight were significantly higher in the ESCC + HMB group than those in the ESCC control group (grip strength, P=0.03; gastrocnemius muscle weight, P<0.01). No significant difference in grip strength or gastrocnemius muscle weight was observed between the ESCC + HMB and non-tumor groups (grip strength, P=0.94; gastrocnemius muscle weight, P=0.65). No difference in grip strength or gastrocnemius muscle weight was observed between non-tumor mice and ESCC mice (grip strength: P=0.35, gastrocnemius muscle weight: P=0.37). CONCLUSIONS: HMB administration to ESCC-bearing mice maintained grip strength and gastrocnemius muscle weight at levels comparable to those of non-transplanted (non-ESCC) mice. Future studies should elucidate the mechanisms by which HMB counteracts cachexia and confirm these physiological findings with molecular biological evidence.