title: Potential role for the VDR agonist elocalcitol in metabolic control: Evidences in human skeletal muscle cells.
abstract: Vitamin D plays a pivotal role to maintain skeletal muscle integrity and health. Vitamin D deficiency characterizes inflammatory myopathy (IM) and diabetes, often overlapping diseases involving skeletal muscle damage. Vitamin D receptor (VDR) agonists likely exert beneficial effects in both IM and metabolic disturbances. We aim to evaluate in vitro the effect of elocalcitol, a non-hypercalcemic VDR agonist, on the biomolecular metabolic machinery of human skeletal muscle cells (Hfsmc), vs. insulin (I). We analyzed GLUT4, Flotillin-1, Caveolin-3 and Caveolin-1 cell expression/localization; mTOR, AKT, ERK and 4E-BP1 phosphorylation; IL-6 myokine release; VDR expression. We investigated in vivo vitamin D status in IM subjects, evaluating VDR muscular expression and serum vitamin D with metabolism-related parameters, as glycemia, triglycerides, cholesterol, resistin and adiponectin. In Hfsmc, elocalcitol exerted an I-like effect, promoting GLUT4 re-localization in Flotillin-1, Caveolin-3 and Caveolin-1 positive sites and mTOR, AKT, ERK, 4E-BP1 activation; it enhanced IL-6 myokine release. IM subjects, all normoglycemic, showed VDR/vitamin D deficiency that, together with high lipidemic and resistin profile, possibly increases the risk to develop metabolic diseases. VDR agonists as elocalcitol may be therapeutic tools for skeletal muscle integrity/function maintenance, an indispensable condition for health homeostasis.
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Antinozzi
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy; Leeds Institute of Rheumatic & Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Corinaldesi
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Annalinda
authors.initials: A
authors.lastname: Pisano
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Cerbelli
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Migliaccio
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Luigi
authors.affiliation: Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Stefanantoni
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors.forename: Gabriella Barbara
authors.initials: GB
authors.lastname: Vannelli
authors.affiliation: Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Minisola
authors.affiliation: Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.affiliation: Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy. Electronic address: clara.crescioli@uniroma4.it.
authors.forename: Clara
authors.initials: C
authors.lastname: Crescioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000196:embryology; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000378:metabolism*; D052243:Resistin / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism; D055815:Young Adult
chemical_list: C487049:BXL628; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D008055:Lipids; C499624:RETN protein, human; D018167:Receptors, Calcitriol; D052243:Resistin; C579457:VDR protein, human; D014807:Vitamin D; D002117:Calcitriol
keywords: Human skeletal muscle cells; Inflammatory myopathy; Metabolism; VDR agonist