(-)-Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy.
Adult
Biopsy
Blotting, Western
Catechin
/ therapeutic use
Creatine Kinase
/ metabolism
Dysferlin
/ metabolism
Exercise Test
Follistatin
/ metabolism
Heart Rate
Humans
Lactic Acid
/ blood
MEF2 Transcription Factors
/ metabolism
Male
Microscopy, Electron
Middle Aged
Mitochondria
/ ultrastructure
Mitochondrial Proteins
/ metabolism
Mitochondrial Size
Muscle Proteins
/ metabolism
Muscle Strength
Muscle, Skeletal
/ metabolism
Muscular Dystrophy, Duchenne
/ drug therapy
MyoD Protein
/ metabolism
Myogenic Regulatory Factor 5
/ metabolism
Myogenin
/ metabolism
Myostatin
/ metabolism
Organelle Biogenesis
Oxygen Consumption
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ metabolism
Regeneration
Utrophin
/ metabolism
aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin
Journal
Muscle & nerve
ISSN: 1097-4598
Titre abrégé: Muscle Nerve
Pays: United States
ID NLM: 7803146
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
04
08
2019
revised:
22
10
2020
accepted:
25
10
2020
pubmed:
31
10
2020
medline:
16
3
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
We conducted an open-label study to examine the effects of the flavonoid (-)-epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Seven participants received (-)-epicatechin 50 mg twice per day for 8 weeks. Pre- and postprocedures included biceps brachii biopsy to assess muscle structure and growth-relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests. Western blotting showed significantly increased levels of enzymes modulating cellular bioenergetics (liver kinase B1 and 5'-adenosine monophosphate-activated protein kinase). Peroxisome proliferator-activated receptor gamma coactivator-1alpha, a transcriptional coactivator of genes involved in mitochondrial biogenesis and cristae-associated mitofilin levels, increased as did cristae abundance. Muscle and plasma follistatin increased significantly while myostatin decreased. Markers of skeletal muscle regeneration myogenin, myogenic regulatory factor-5, myoblast determination protein 1, myocyte enhancer factor-2, and structure-associated proteins, including dysferlin, utrophin, and intracellular creatine kinase, also increased. Exercise testing demonstrated decreased heart rate, maximal oxygen consumption per kilogram, and plasma lactate levels at defined workloads. Tissue saturation index improved in resting and postexercise states. (-)-Epicatechin, an exercise mimetic, appears to have short-term positive effects on tissue biomarkers indicative of mitochondrial biogenesis and muscle regeneration, and produced improvements in graded exercise testing parameters in patients with BMD.
Identifiants
pubmed: 33125736
doi: 10.1002/mus.27108
pmc: PMC7898288
doi:
Substances chimiques
Dysferlin
0
Follistatin
0
IMMT protein, human
0
MEF2 Transcription Factors
0
Mitochondrial Proteins
0
Muscle Proteins
0
MyoD Protein
0
MyoD1 myogenic differentiation protein
0
Myogenic Regulatory Factor 5
0
Myogenin
0
Myostatin
0
PPARGC1A protein, human
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Utrophin
0
Lactic Acid
33X04XA5AT
Catechin
8R1V1STN48
Creatine Kinase
EC 2.7.3.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
239-249Subventions
Organisme : NIGMS NIH HHS
ID : R24 GM137200
Pays : United States
Informations de copyright
© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
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