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Nutrition. 2014 Jul-Aug;30(7-8):807-13. doi: 10.1016/j.nut.2013.11.012. Epub 2013 Dec 4.

Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia.

Author information

1
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom. Electronic address: K.a.mirza@aston.ac.uk.
2
Abbott Nutrition, Research & Development, Columbus, Ohio, USA.
3
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.

Abstract

OBJECTIVE:

Loss of skeletal muscle is the most debilitating feature of cancer cachexia, and there are few treatments available. The aim of this study was to compare the anticatabolic efficacy of L-leucine and the leucine metabolite β-hydroxy-β-methylbutyrate (Ca-HMB) on muscle protein metabolism, both in vitro and in vivo.

METHODS:

Studies were conducted in mice bearing the cachexia-inducing murine adenocarcinoma 16 tumor, and in murine C2 C12 myotubes exposed to proteolysis-inducing factor, lipopolysaccharide, and angiotensin II.

RESULTS:

Both leucine and HMB were found to attenuate the increase in protein degradation and the decrease in protein synthesis in murine myotubes induced by proteolysis-inducing factor, lipopolysaccharide, and angiotensin II. However, HMB was more potent than leucine, because HMB at 50 μM produced essentially the same effect as leucine at 1 mM. Both leucine and HMB reduced the activity of the ubiquitin-proteasome pathway as measured by the functional (chymotrypsin-like) enzyme activity of the proteasome in muscle lysates, as well as Western blot quantitation of protein levels of the structural/enzymatic proteasome subunits (20 S and 19 S) and the ubiquitin ligases (MuRF1 and MAFbx). In vivo studies in mice bearing the murine adenocarcinoma 16 tumor showed a low dose of Ca-HMB (0.25 g/kg) to be 60% more effective than leucine (1 g/kg) in attenuating loss of body weight over a 4-d period.

CONCLUSION:

These results favor the clinical feasibility of using Ca-HMB over high doses of leucine for the treatment of cancer cachexia.

KEYWORDS:

L-Leucine; Muscle; Protein degradation; Protein synthesis; β-hydroxy-β-methylbutyrate, HMB

PMID:
24984997
DOI:
10.1016/j.nut.2013.11.012
[Indexed for MEDLINE]

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