title: Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle.
abstract: Supra-physiological levels of vitamin D induce skeletal muscle atrophy, which may be particularly detrimental in already sarcopaenic elderly. Neither the cause nor whether the atrophy is fibre type specific are known. To obtain supraphysiological levels of circulating vitamin D (1,25(OH)(2)D(3)) 27.5-month-old female Fischer(344) × Brown Norway F1 rats were orally treated for 6 weeks with vehicle or the vitamin D analogue alfacalcidol. Alfacalcidol treatment induced a 22% decrease in body mass and 17% muscle atrophy. Fibre atrophy was restricted to type IIb fibres in the low-oxidative part of the gastrocnemius medialis only (-22%; P < 0.05). There was a concomitant 1.6-fold increase in mRNA expression of the ubiquitin ligase MuRF-1 (P < 0.001), whereas those of insulin-like growth factor 1 and myostatin were not affected. Circulating IL-6 was unaltered, but leptin and adiponectin were decreased (-39%) and increased (64%), respectively. The treated rats also exhibited a reduced food intake. In conclusion, supraphysiological levels of circulating 1,25(OH)(2)D(3) cause preferential atrophy of type IIb fibres, which is associated with an increased expression of MuRF-1 without evidence of systemic inflammation. The atrophy and loss of body mass in the presence of supra-physiological levels of vitamin D are primarily due to a reduced food intake.
authors: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, John Dalton Building, Oxford Road, Manchester, M5 1GD, UK.
authors: Janwillem
authors: J
authors: Testerink
authors: Richard T
authors: RT
authors: Jaspers
authors: Jörn
authors: J
authors: Rittweger
authors: Arnold
authors: A
authors: de Haan
authors: Hans
authors: H
authors: Degens
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D015992:Body Mass Index; D019587:Dietary Supplements; D004435:Eating / Q000187:drug effects; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007249:Inflammation / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood*; D020738:Leptin / Q000097:blood; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D006887:Hydroxycholecalciferols; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D020738:Leptin; D009124:Muscle Proteins; D055435:Myostatin; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D014807:Vitamin D; D007334:Insulin-Like Growth Factor I; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; C008088:alfacalcidol