Skeletal muscle
atrophy and whole-body
glucose intolerance are consequences of muscle disuse associated with conditions leading to prolonged
bed rest. Nutritional supplementation with
chromium has been shown to prevent
weight loss and improve
glucose tolerance in malnourished subjects on long-term
total parenteral nutrition. The objective of this study was to evaluate the effect of oral supplementation with a novel
chromium complex,
chromium (d-phenylalanine)(3) [Cr(d-phe)(3)] at 45 microg/kg/day for 5 weeks, on skeletal muscle
atrophy and
glucose intolerance in a hindlimb suspension mouse model. Hindlimb-suspended mice exhibited reduced skeletal muscle fiber size and enhanced whole-body
glucose intolerance, both of which were reversed by
chromium treatment. The inhibition of skeletal muscle
atrophy by
chromium was associated with reductions in the ubiquitination
ligase atrogin-1/
muscle atrophy F-box, which is elevated in hindlimb-suspended mice. Neither hindlimb suspension nor
chromium treatment altered the
protein levels of the
myostatin, phospho-Forkhead box O-1 and
mammalian target of rapamycin.
Chromium-treated animals exhibited elevated Akt (Homo sapiens v-akt murine
thymoma viral oncogene homolog) phosphorylation in their skeletal muscle, with no change observed in the levels of activated JNK (
c-Jun N-terminal kinase). Thus, these data suggest that nutritional supplementation with
chromium may have potential therapeutic benefits in minimizing skeletal muscle
atrophy associated with long periods of muscle disuse.