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J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):583-597. doi: 10.1002/jcsm.12190. Epub 2017 Mar 1.

Urolithin B, a newly identified regulator of skeletal muscle mass.

Author information

1
Institute of Neuroscience, Université catholique de Louvain, 1 place Pierre de Coubertin, 1348, Louvain-la-Neuve, Belgium.
2
PROCELL nutrition sprl, 2 Rue Jean Burgers, 7850, Enghien, Belgium.
3
De Duve Institute, Université catholique de Louvain, 75 Avenue Hippocrate, 1200, Brussels, Belgium.
4
Department of Biomolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, University of Mississippi, Medicinal Plant Garden, RM 104, University, MS, 38677, USA.

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.

KEYWORDS:

Androgen receptor; Hypertrophy; Polyphenols; mTORC1 signalling

PMID:
28251839
PMCID:
PMC5566634
DOI:
10.1002/jcsm.12190
[Indexed for MEDLINE]
Free PMC Article

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