title: Urolithin B, a newly identified regulator of skeletal muscle mass.
abstract: BACKGROUND
  The control of muscle size is an essential feature of health. Indeed, skeletal muscle atrophy leads to reduced strength, poor quality of life, and metabolic disturbances. Consequently, strategies aiming to attenuate muscle wasting and to promote muscle growth during various (pathological) physiological states like sarcopenia, immobilization, malnutrition, or cachexia are needed to address this extensive health issue. In this study, we tested the effects of urolithin B, an ellagitannin-derived metabolite, on skeletal muscle growth.
  
  
  METHODS
  C2C12 myotubes were treated with 15 μM of urolithin B for 24 h. For in vivo experiments, mice were implanted with mini-osmotic pumps delivering continuously 10 μg/day of urolithin B during 28 days. Muscle atrophy was studied in mice with a sciatic nerve denervation receiving urolithin B by the same way.
  
  
  RESULTS
  Our experiments reveal that urolithin B enhances the growth and differentiation of C2C12 myotubes by increasing protein synthesis and repressing the ubiquitin-proteasome pathway. Genetic and pharmacological arguments support an implication of the androgen receptor. Signalling analyses suggest a crosstalk between the androgen receptor and the mTORC1 pathway, possibly via AMPK. In vivo experiments confirm that urolithin B induces muscle hypertrophy in mice and reduces muscle atrophy after the sciatic nerve section.
  
  
  CONCLUSIONS
  This study highlights the potential usefulness of urolithin B for the treatment of muscle mass loss associated with various (pathological) physiological states.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.|PROCELL nutrition sprl, 2 Rue Jean Burgers, 7850, Enghien, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pierre
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Damien
authors.initials: D
authors.lastname: Naslain
authors.affiliation: De Duve Institute, Université catholique de Louvain, 75 Avenue Hippocrate, 1200, Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Bontemps
authors.affiliation: Department of Biomolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, University of Mississippi, Medicinal Plant Garden, RM 104, University, MS, 38677, USA.
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: PROCELL nutrition sprl, 2 Rue Jean Burgers, 7850, Enghien, Belgium.
authors.forename: Fabian
authors.initials: F
authors.lastname: Priem
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D003374:Coumarins; D009124:Muscle Proteins; D011944:Receptors, Androgen; C000595064:urolithin B; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Androgen receptor; Hypertrophy; Polyphenols; mTORC1 signalling