title: Vitamin D3 intake modulates diaphragm but not peripheral muscle force in young mice.
abstract: Recent data support an important role for vitamin D in respiratory health. We tested the hypothesis that dietary vitamin D3 (VD3) intake modulates diaphragm (DIA) strength. Four-week-old female A/J mice (n = 10/group) were randomized to receive diets containing 100 IU VD3/kg (low), 1,000 IU VD3/kg (reference), or 10,000 IU VD3/kg (pharmacologic). After 6 wk of dietary intervention, plasma 25-hydroxyvitamin D3 (25D3) levels, DIA and extensor digitorum longus (EDL) in vitro contractile properties, and fiber cross-sectional area (CSA) were measured. Myosin heavy chain (MHC) composition and Akt/Foxo3A growth signaling were studied in the DIA and tibialis anterior. Mice fed the low, reference, and pharmacologic diets had average 25D3 levels of 7, 21, and 59 ng/ml, respectively. Maximal DIA force, twitch force, and fiber CSA were reduced 26%, 28%, and 10% (P < 0.01), respectively, in mice receiving the low-VD3 diet compared with the reference and pharmacologic diets. EDL force parameters were unaltered by diet. Effects of VD3 intake on DIA force were not observed in mice that began dietary intervention at 12 wk of age. VD3 intake did not alter the MHC composition of the DIA, indicating that decreases in force and CSA in young mice were not due to a switch in fiber type. Paradoxically, low VD3 intake was associated with activation of anabolic signaling in muscle (hyperphosphorylation of Akt and Foxo3A and decreased expression of autophagy marker LC3). These studies identify a potential role of dietary VD3 in regulating DIA development and insulin sensitivity.
authors.affiliation: Department of Rehabilitation Science, University at Buffalo, Buffalo, New York; adr@buffalo.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Ray
authors.affiliation: Department of Rehabilitation Science, University at Buffalo, Buffalo, New York;
authors.forename: Kirkwood E
authors.initials: KE
authors.lastname: Personius
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York;
authors.forename: David L
authors.initials: DL
authors.lastname: Williamson
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York;
authors.forename: Cory M
authors.initials: CM
authors.lastname: Dungan
authors.affiliation: Department of Medicine, Thoracic Oncology, Roswell Park Cancer Institute, Buffalo, New York; and.
authors.forename: Samjot S
authors.initials: SS
authors.lastname: Dhillon
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Hershberger
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002112:Calcifediol / Q000008:administration & dosage*; D003964:Diaphragm / Q000378:metabolism / Q000502:physiology*; D004032:Diet; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000071316:Forkhead Box Protein O3; D008869:Microtubule-Associated Proteins; D051057:Proto-Oncogene Proteins c-akt; D018995:Myosin Heavy Chains; D002112:Calcifediol
keywords: diaphragm; fatigue; force; vitamin D