(−)‐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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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 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7898288</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2456413120</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4438-d1146355be5f9a72021923347c647984351aacfe2b29314fcfd1c55ad84909a03</originalsourceid><addsrcrecordid>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</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2479383391</pqid></control><display><type>article</type><title>(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy</title><source>Wiley</source><source>MEDLINE</source><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.</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 & 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 & 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 & 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”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4438-d1146355be5f9a72021923347c647984351aacfe2b29314fcfd1c55ad84909a03</citedby><cites>FETCH-LOGICAL-c4438-d1146355be5f9a72021923347c647984351aacfe2b29314fcfd1c55ad84909a03</cites><orcidid>0000-0002-1725-9866 ; 0000-0002-8779-3220 ; 0000-0002-7511-6441 ; 0000-0002-3251-4909 ; 0000-0003-2155-3934</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmus.27108$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmus.27108$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33125736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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. 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 & 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. Ted</creator><creator>Villarreal, Francisco</creator><creator>Ceballos, Guillermo</creator><creator>Perkins, Guy</creator><creator>Dugar, Sundeep</creator><creator>Schreiner, George</creator><creator>Henricson, Erik K.</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TS</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><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></search><sort><creationdate>202102</creationdate><title>(−)‐Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy</title><author>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.</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. 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><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Muscle & nerve</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McDonald, Craig M.</au><au>Ramirez‐Sanchez, Israel</au><au>Oskarsson, Björn</au><au>Joyce, Nanette</au><au>Aguilar, Candace</au><au>Nicorici, Alina</au><au>Dayan, Jonathan</au><au>Goude, Erica</au><au>Abresch, R. 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 & 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 & 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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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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