(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy

Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods Seven participants received (−)‐epicatechin 50 mg twice per day for 8 weeks. Pre‐ and postprocedures included biceps...

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Veröffentlicht in:Muscle & nerve 2021-02, Vol.63 (2), p.239-249
Hauptverfasser: McDonald, Craig M., Ramirez‐Sanchez, Israel, Oskarsson, Björn, Joyce, Nanette, Aguilar, Candace, Nicorici, Alina, Dayan, Jonathan, Goude, Erica, Abresch, R. Ted, Villarreal, Francisco, Ceballos, Guillermo, Perkins, Guy, Dugar, Sundeep, Schreiner, George, Henricson, Erik K.
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container_end_page 249
container_issue 2
container_start_page 239
container_title Muscle & nerve
container_volume 63
creator McDonald, Craig M.
Ramirez‐Sanchez, Israel
Oskarsson, Björn
Joyce, Nanette
Aguilar, Candace
Nicorici, Alina
Dayan, Jonathan
Goude, Erica
Abresch, R. Ted
Villarreal, Francisco
Ceballos, Guillermo
Perkins, Guy
Dugar, Sundeep
Schreiner, George
Henricson, Erik K.
description Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods 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. Results 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. Discussion (−)‐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.
doi_str_mv 10.1002/mus.27108
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Ted ; Villarreal, Francisco ; Ceballos, Guillermo ; Perkins, Guy ; Dugar, Sundeep ; Schreiner, George ; Henricson, Erik K.</creator><creatorcontrib>McDonald, Craig M. ; Ramirez‐Sanchez, Israel ; Oskarsson, Björn ; Joyce, Nanette ; Aguilar, Candace ; Nicorici, Alina ; Dayan, Jonathan ; Goude, Erica ; Abresch, R. Ted ; Villarreal, Francisco ; Ceballos, Guillermo ; Perkins, Guy ; Dugar, Sundeep ; Schreiner, George ; Henricson, Erik K.</creatorcontrib><description>Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods 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. Results 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. Discussion (−)‐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.</description><identifier>ISSN: 0148-639X</identifier><identifier>ISSN: 1097-4598</identifier><identifier>EISSN: 1097-4598</identifier><identifier>DOI: 10.1002/mus.27108</identifier><identifier>PMID: 33125736</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>Adenosine kinase ; Adenosine monophosphate ; Adult ; aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin ; AMP ; Becker's muscular dystrophy ; Bioenergetics ; Biomarkers ; Biopsy ; Biosynthesis ; Blotting, Western ; Catechin - therapeutic use ; Clinical ; Clinical s ; Creatine ; Creatine kinase ; Creatine Kinase - metabolism ; Cristae ; Dysferlin - metabolism ; Dystrophy ; Electron microscopy ; Epicatechin ; Exercise Test ; Flavonoids ; Follistatin ; Follistatin - metabolism ; Heart Rate ; Hepatocytes ; Humans ; Kinases ; Lactic acid ; Lactic Acid - blood ; Male ; MEF2 Transcription Factors - metabolism ; Microscopy, Electron ; Middle Aged ; Mitochondria ; Mitochondria - ultrastructure ; Mitochondrial Proteins - metabolism ; Mitochondrial Size ; Muscle Proteins - metabolism ; Muscle Strength ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - physiopathology ; Muscle, Skeletal - ultrastructure ; Muscular dystrophy ; Muscular Dystrophy, Duchenne - drug therapy ; Muscular Dystrophy, Duchenne - metabolism ; Muscular Dystrophy, Duchenne - pathology ; Muscular Dystrophy, Duchenne - physiopathology ; Myoblasts ; Myocytes ; MyoD Protein - metabolism ; Myogenic Regulatory Factor 5 - metabolism ; Myogenin ; Myogenin - metabolism ; Myostatin ; Myostatin - metabolism ; Organelle Biogenesis ; Oxygen Consumption ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism ; Physical training ; Protein kinase ; Proteins ; Regeneration ; Saturation index ; Skeletal muscle ; Transcription ; Utrophin - metabolism ; Volume measurement ; Western blotting</subject><ispartof>Muscle &amp; nerve, 2021-02, Vol.63 (2), p.239-249</ispartof><rights>2020 The Authors. published by Wiley Periodicals LLC.</rights><rights>2020 The Authors. Muscle &amp; Nerve published by Wiley Periodicals LLC.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). 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Ted</creatorcontrib><creatorcontrib>Villarreal, Francisco</creatorcontrib><creatorcontrib>Ceballos, Guillermo</creatorcontrib><creatorcontrib>Perkins, Guy</creatorcontrib><creatorcontrib>Dugar, Sundeep</creatorcontrib><creatorcontrib>Schreiner, George</creatorcontrib><creatorcontrib>Henricson, Erik K.</creatorcontrib><title>(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy</title><title>Muscle &amp; nerve</title><addtitle>Muscle Nerve</addtitle><description>Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods 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. Results 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. Discussion (−)‐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.</description><subject>Adenosine kinase</subject><subject>Adenosine monophosphate</subject><subject>Adult</subject><subject>aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin</subject><subject>AMP</subject><subject>Becker's muscular dystrophy</subject><subject>Bioenergetics</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Biosynthesis</subject><subject>Blotting, Western</subject><subject>Catechin - therapeutic use</subject><subject>Clinical</subject><subject>Clinical s</subject><subject>Creatine</subject><subject>Creatine kinase</subject><subject>Creatine Kinase - metabolism</subject><subject>Cristae</subject><subject>Dysferlin - metabolism</subject><subject>Dystrophy</subject><subject>Electron microscopy</subject><subject>Epicatechin</subject><subject>Exercise Test</subject><subject>Flavonoids</subject><subject>Follistatin</subject><subject>Follistatin - metabolism</subject><subject>Heart Rate</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lactic acid</subject><subject>Lactic Acid - blood</subject><subject>Male</subject><subject>MEF2 Transcription Factors - metabolism</subject><subject>Microscopy, Electron</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondria - ultrastructure</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Mitochondrial Size</subject><subject>Muscle Proteins - metabolism</subject><subject>Muscle Strength</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - physiopathology</subject><subject>Muscle, Skeletal - ultrastructure</subject><subject>Muscular dystrophy</subject><subject>Muscular Dystrophy, Duchenne - drug therapy</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Muscular Dystrophy, Duchenne - pathology</subject><subject>Muscular Dystrophy, Duchenne - physiopathology</subject><subject>Myoblasts</subject><subject>Myocytes</subject><subject>MyoD Protein - metabolism</subject><subject>Myogenic Regulatory Factor 5 - metabolism</subject><subject>Myogenin</subject><subject>Myogenin - metabolism</subject><subject>Myostatin</subject><subject>Myostatin - metabolism</subject><subject>Organelle Biogenesis</subject><subject>Oxygen Consumption</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism</subject><subject>Physical training</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Regeneration</subject><subject>Saturation index</subject><subject>Skeletal muscle</subject><subject>Transcription</subject><subject>Utrophin - metabolism</subject><subject>Volume measurement</subject><subject>Western blotting</subject><issn>0148-639X</issn><issn>1097-4598</issn><issn>1097-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kU1PFTEUhhujkSu48A-YJm5gMdDPabsxUQJognGBJO6a3rbDFGeml3ZGcncsWRp_Ir-EjheJmrg6i_PkOR8vAK8w2scIkYN-yvtEYCSfgAVGSlSMK_kULBBmsqqp-roFXuR8iRDCshbPwRalmHBB6wW42b27_bl3d_PjaBWsGb1twwDD4CbrM-zDGG0bB5eC6eAyxAs_-BwyNIODvUnffMowNrDMt52Hyc_9ZMYQZwc0burGDK_D2ML33hb6Fzl1JkG3zmOKq3a9A541psv-5UPdBufHR18OP1Snn08-Hr47rSxjVFYOY1ZTzpeeN8oIgghWhFImbM2EkoxybIxtPFkSRTFrbOOw5dw4yRRSBtFt8HbjXU3L3jvrhzGZTq9SKIesdTRB_90ZQqsv4nctpJJEyiLYfRCkeDX5POo-ZOu7zgw-TlkTxmuGy2PnWW_-QS_jlIZyXqGEopJShQu1t6Fsijkn3zwug5Gec9X9rJ1zLezrP7d_JH8HWYCDDXAdOr_-v0l_Oj_bKO8BhkyxEA</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>McDonald, Craig M.</creator><creator>Ramirez‐Sanchez, Israel</creator><creator>Oskarsson, Björn</creator><creator>Joyce, Nanette</creator><creator>Aguilar, Candace</creator><creator>Nicorici, Alina</creator><creator>Dayan, Jonathan</creator><creator>Goude, Erica</creator><creator>Abresch, R. 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Ted ; Villarreal, Francisco ; Ceballos, Guillermo ; Perkins, Guy ; Dugar, Sundeep ; Schreiner, George ; Henricson, Erik K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4438-d1146355be5f9a72021923347c647984351aacfe2b29314fcfd1c55ad84909a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine kinase</topic><topic>Adenosine monophosphate</topic><topic>Adult</topic><topic>aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin</topic><topic>AMP</topic><topic>Becker's muscular dystrophy</topic><topic>Bioenergetics</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Biosynthesis</topic><topic>Blotting, Western</topic><topic>Catechin - therapeutic use</topic><topic>Clinical</topic><topic>Clinical s</topic><topic>Creatine</topic><topic>Creatine kinase</topic><topic>Creatine Kinase - metabolism</topic><topic>Cristae</topic><topic>Dysferlin - metabolism</topic><topic>Dystrophy</topic><topic>Electron microscopy</topic><topic>Epicatechin</topic><topic>Exercise Test</topic><topic>Flavonoids</topic><topic>Follistatin</topic><topic>Follistatin - metabolism</topic><topic>Heart Rate</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Kinases</topic><topic>Lactic acid</topic><topic>Lactic Acid - blood</topic><topic>Male</topic><topic>MEF2 Transcription Factors - metabolism</topic><topic>Microscopy, Electron</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondria - ultrastructure</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitochondrial Size</topic><topic>Muscle Proteins - metabolism</topic><topic>Muscle Strength</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - physiopathology</topic><topic>Muscle, Skeletal - ultrastructure</topic><topic>Muscular dystrophy</topic><topic>Muscular Dystrophy, Duchenne - drug therapy</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Muscular Dystrophy, Duchenne - pathology</topic><topic>Muscular Dystrophy, Duchenne - physiopathology</topic><topic>Myoblasts</topic><topic>Myocytes</topic><topic>MyoD Protein - metabolism</topic><topic>Myogenic Regulatory Factor 5 - metabolism</topic><topic>Myogenin</topic><topic>Myogenin - metabolism</topic><topic>Myostatin</topic><topic>Myostatin - metabolism</topic><topic>Organelle Biogenesis</topic><topic>Oxygen Consumption</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism</topic><topic>Physical training</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Regeneration</topic><topic>Saturation index</topic><topic>Skeletal muscle</topic><topic>Transcription</topic><topic>Utrophin - metabolism</topic><topic>Volume measurement</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McDonald, Craig M.</creatorcontrib><creatorcontrib>Ramirez‐Sanchez, Israel</creatorcontrib><creatorcontrib>Oskarsson, Björn</creatorcontrib><creatorcontrib>Joyce, Nanette</creatorcontrib><creatorcontrib>Aguilar, Candace</creatorcontrib><creatorcontrib>Nicorici, Alina</creatorcontrib><creatorcontrib>Dayan, Jonathan</creatorcontrib><creatorcontrib>Goude, Erica</creatorcontrib><creatorcontrib>Abresch, R. 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Ted</au><au>Villarreal, Francisco</au><au>Ceballos, Guillermo</au><au>Perkins, Guy</au><au>Dugar, Sundeep</au><au>Schreiner, George</au><au>Henricson, Erik K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy</atitle><jtitle>Muscle &amp; nerve</jtitle><addtitle>Muscle Nerve</addtitle><date>2021-02</date><risdate>2021</risdate><volume>63</volume><issue>2</issue><spage>239</spage><epage>249</epage><pages>239-249</pages><issn>0148-639X</issn><issn>1097-4598</issn><eissn>1097-4598</eissn><abstract>Introduction We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Methods 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. Results 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. Discussion (−)‐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.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>33125736</pmid><doi>10.1002/mus.27108</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-1725-9866</orcidid><orcidid>https://orcid.org/0000-0002-8779-3220</orcidid><orcidid>https://orcid.org/0000-0002-7511-6441</orcidid><orcidid>https://orcid.org/0000-0002-3251-4909</orcidid><orcidid>https://orcid.org/0000-0003-2155-3934</orcidid><oa>free_for_read</oa></addata></record>
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source Wiley; MEDLINE
subjects Adenosine kinase
Adenosine monophosphate
Adult
aerobic exercise, Becker muscular dystrophy, epicatechin, mitochondrial biogenesis follistatin
AMP
Becker's muscular dystrophy
Bioenergetics
Biomarkers
Biopsy
Biosynthesis
Blotting, Western
Catechin - therapeutic use
Clinical
Clinical s
Creatine
Creatine kinase
Creatine Kinase - metabolism
Cristae
Dysferlin - metabolism
Dystrophy
Electron microscopy
Epicatechin
Exercise Test
Flavonoids
Follistatin
Follistatin - metabolism
Heart Rate
Hepatocytes
Humans
Kinases
Lactic acid
Lactic Acid - blood
Male
MEF2 Transcription Factors - metabolism
Microscopy, Electron
Middle Aged
Mitochondria
Mitochondria - ultrastructure
Mitochondrial Proteins - metabolism
Mitochondrial Size
Muscle Proteins - metabolism
Muscle Strength
Muscle, Skeletal - metabolism
Muscle, Skeletal - physiopathology
Muscle, Skeletal - ultrastructure
Muscular dystrophy
Muscular Dystrophy, Duchenne - drug therapy
Muscular Dystrophy, Duchenne - metabolism
Muscular Dystrophy, Duchenne - pathology
Muscular Dystrophy, Duchenne - physiopathology
Myoblasts
Myocytes
MyoD Protein - metabolism
Myogenic Regulatory Factor 5 - metabolism
Myogenin
Myogenin - metabolism
Myostatin
Myostatin - metabolism
Organelle Biogenesis
Oxygen Consumption
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Physical training
Protein kinase
Proteins
Regeneration
Saturation index
Skeletal muscle
Transcription
Utrophin - metabolism
Volume measurement
Western blotting
title (−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy
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