Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice.
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.
Dong
Feng
F
School of Pharmacy, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
Hua
Yinan
Y
Zhao
Peng
P
Ren
Jun
J
Du
Min
M
Sreejayan
Nair
N
D000818:Animals; D002857:Chromium / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005951:Glucose Tolerance Test; D019417:Hindlimb Suspension; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D009942:Organometallic Compounds; C512471:chromium (D-Phenylalanine)3; D002857:Chromium; D010649:Phenylalanine; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases