β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia

Abstract

Abstract. ß-hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMBenriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2·, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2· markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2· levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.

β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy

“…Although HMB may protect skeletal muscle from the catabolic effects of cancer cachexia [12–14], AIDS [15], aging [18], muscular dystrophy [29], endotoxemia [16,17], and glucocorticoids (present study), the protective effects of HMB are not universal. For example, in a controlled clinical trial, HMB (in combination with glutamine and arginine) did not prevent muscle wasting in patients with rheumatoid arthritis [30].…”

“…Previous studies suggest that β-hydroxy-β-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine, may attenuate the loss of muscle mass caused by cancer cachexia [12–14], AIDS [15], endotoxemia [16,17], and aging [18] and that this effect of HMB reflects inhibited protein degradation and/or stimulated protein synthesis. Other reports suggest that the MAP kinase and PI3K/Akt signaling pathways are involved in the beneficial effects of HMB in skeletal muscle [17,19–21].…”

Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour

“…These data suggest that the foetuses that received nutritional leucine supplementation, even those that were suffering from their mother’s tumours, showed diminished deleterious effects due to tumour growth compared to those that did not receive leucine; the foetuses in the LW group had similar muscle protein synthesis to the control foetuses, and more importantly, the process of protein catabolism was minimised and was equal to that of the control group [4,5,54]. Further studies are underway in our laboratory to determine whether leucine supplementation can counteract the damage to foetal growth during cancer development and the mechanism underlying this effect.…”

Cancer-induced muscle wasting: latest findings in prevention and treatment

“…41–43 The therapeutic role of HMB in human cancer cachexia, however, is still uncertain and deserves further investigation, as was noted in a recent systematic review on this topic. 44 …”