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

Kamran A. Mirza, Suzette L. Pereira, Anne C. Voss, Michael J. Tisdale

Research output: Contribution to journalArticle

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 invitro and invivo.

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). Invivo studies in mice bearing the murine adenocarcinoma 16 tumor showed a low dose of Ca-HMB (0.25 g/kg) tobe 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.

LanguageEnglish
Pages807-813
Number of pages7
JournalNutrition
Volume30
Issue number7-8
Early online date4 Dec 2013
DOIs
Publication statusPublished - Jul 2014

Fingerprint

Cachexia
Leucine
Theoretical Models
Neoplasms
Proteasome Endopeptidase Complex
Proteolysis
Skeletal Muscle Fibers
Ubiquitin
Angiotensin II
Lipopolysaccharides
Adenocarcinoma
beta-hydroxyisovaleric acid
Muscle Proteins
Ligases
Skeletal Muscle
Proteins
Western Blotting
Body Weight
Muscles

Keywords

  • L-Leucine
  • muscle
  • protein degradation
  • protein synthesis
  • β-hydroxy-β-methylbutyrate, HMB

Cite this

Mirza, Kamran A. ; Pereira, Suzette L. ; Voss, Anne C. ; Tisdale, Michael J. / Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia. In: Nutrition. 2014 ; Vol. 30, No. 7-8. pp. 807-813.
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Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia. / Mirza, Kamran A.; Pereira, Suzette L.; Voss, Anne C.; Tisdale, Michael J.

In: Nutrition, Vol. 30, No. 7-8, 07.2014, p. 807-813.

Research output: Contribution to journalArticle

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AU - Tisdale, Michael J.

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