{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:03:19Z","timestamp":1791050599385,"version":"4.1.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2016,6,21]],"date-time":"2016-06-21T00:00:00Z","timestamp":1466467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R9320118974"],"award-info":[{"award-number":["R9320118974"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001825","name":"Styrelsen for Forskning og Innovation","doi-asserted-by":"publisher","award":["DFF-1323-00317"],"award-info":[{"award-number":["DFF-1323-00317"]}],"id":[{"id":"10.13039\/501100001825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0156460","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T20:02:47Z","timestamp":1466625767000},"page":"e0156460","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Lack of Skeletal Muscle IL-6 Affects Pyruvate Dehydrogenase Activity at Rest and during Prolonged Exercise"],"prefix":"10.1371","volume":"11","author":[{"given":"Anders","family":"Gudiksen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla Lindgren","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e6rke","family":"Bertholdt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Joensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob G.","family":"Knudsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette","family":"Pilegaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,6,21]]},"reference":[{"key":"ref1","first-page":"E268","article-title":"Fatty acid oxidation is directly regulated by carbohydrate metabolism during exercise","volume":"273","author":"EF Coyle","year":"1997","journal-title":"Am J Physiol"},{"key":"ref2","first-page":"E380","article-title":"Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration","volume":"265","author":"JA Romijn","year":"1993","journal-title":"Am J Physiol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(63)91500-9","article-title":"The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus","volume":"1","author":"PJ Randle","year":"1963","journal-title":"Lancet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1469-7793.2001.00295.x","article-title":"The effects of increasing exercise intensity on muscle fuel utilisation in humans","volume":"536","author":"LJ van Loon","year":"2001","journal-title":"J Physiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"E813","DOI":"10.1152\/ajpendo.00436.2002","article-title":"Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle","volume":"284","author":"JF Wojtaszewski","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1748-1716.1967.tb03719.x","article-title":"Muscle glycogen during prolonged severe exercise","volume":"71","author":"L Hermansen","year":"1967","journal-title":"Acta Physiol Scand"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1113\/jphysiol.2002.018820","article-title":"Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man","volume":"541","author":"MJ Watt","year":"2002","journal-title":"J Physiol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0065-2571(01)00061-9","article-title":"Regulation of the activity of the pyruvate dehydrogenase complex","volume":"42","author":"RA Harris","year":"2002","journal-title":"Adv Enzyme Regul"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/13813450600935263","article-title":"Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases","volume":"112","author":"MC Sugden","year":"2006","journal-title":"Arch Physiol Biochem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1074\/jbc.M007558200","article-title":"Probing the mechanism of inactivation of human pyruvate dehydrogenase by phosphorylation of three sites","volume":"276","author":"LG Korotchkina","year":"2001","journal-title":"J Biol Chem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0079-6603(01)70013-X","article-title":"Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms","volume":"70","author":"TE Roche","year":"2001","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1152\/japplphysiol.00132.2004","article-title":"Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal muscle during prolonged exercise","volume":"97","author":"MJ Watt","year":"2004","journal-title":"J Appl Physiol (1985)"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0065-2571(00)00020-0","article-title":"Control of pyruvate dehydrogenase kinase gene expression","volume":"41","author":"RA Harris","year":"2001","journal-title":"Adv Enzyme Regul"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/emm.2001.32","article-title":"Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases","volume":"33","author":"MS Patel","year":"2001","journal-title":"Exp Mol Med"},{"key":"ref15","first-page":"E752","article-title":"Pyruvate dehydrogenase activity and acetyl group accumulation during exercise after different diets","volume":"265","author":"CT Putman","year":"1993","journal-title":"Am J Physiol"},{"key":"ref16","first-page":"E380","article-title":"Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration","volume":"265","author":"JA Romijn","year":"1993","journal-title":"Am J Physiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1042\/cs0630087","article-title":"Activation by exercise of human skeletal muscle pyruvate dehydrogenase in vivo","volume":"63","author":"GR Ward","year":"1982","journal-title":"Clin Sci (Lond)"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1152\/japplphysiol.00571.2005","article-title":"Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids","volume":"100","author":"M Mourtzakis","year":"2006","journal-title":"J Appl Physiol (1985)"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.2337\/db06-0152","article-title":"PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion","volume":"55","author":"H Pilegaard","year":"2006","journal-title":"Diabetes"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1152\/ajpendo.00352.2007","article-title":"Regulation of PDH in human arm and leg muscles at rest and during intense exercise","volume":"294","author":"K Kiilerich","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2337\/db09-1032","article-title":"Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle","volume":"59","author":"K Kiilerich","year":"2010","journal-title":"Diabetes"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.2337\/db12-1650","article-title":"Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation","volume":"62","author":"E Jing","year":"2013","journal-title":"Diabetes"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.freeradbiomed.2014.08.001","article-title":"SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells","volume":"76","author":"O Ozden","year":"2014","journal-title":"Free Radic Biol Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.2337\/db12-1261","article-title":"Contraction and AICAR stimulate IL-6 vesicle depletion from skeletal muscle fibers in vivo","volume":"62","author":"HP Lauritzen","year":"2013","journal-title":"Diabetes"},{"issue":"Pt 1","key":"ref25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1469-7793.2000.00237.x","article-title":"Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6","volume":"529","author":"A Steensberg","year":"2000","journal-title":"J Physiol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"E832","DOI":"10.1152\/ajpendo.00328.2010","article-title":"IL-6 selectively stimulates fat metabolism in human skeletal muscle","volume":"299","author":"E Wolsk","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.2337\/db05-1404","article-title":"Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase","volume":"55","author":"AL Carey","year":"2006","journal-title":"Diabetes"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1113\/jphysiol.2002.030437","article-title":"The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle","volume":"546","author":"JW Helge","year":"2003","journal-title":"J Physiol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1113\/expphysiol.2010.056424","article-title":"Interleukin-6 release is higher across arm than leg muscles during whole-body exercise","volume":"96","author":"JW Helge","year":"2011","journal-title":"Exp Physiol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1152\/japplphysiol.00946.2012","article-title":"IL-6 is not essential for exercise-induced increases in glucose uptake","volume":"114","author":"HM O'Neill","year":"2013","journal-title":"J Appl Physiol (1985)"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00424-013-1399-5","article-title":"Effects of IL-6 on pyruvate dehydrogenase regulation in mouse skeletal muscle","volume":"466","author":"RS Bienso","year":"2014","journal-title":"Pflugers Arch"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbrc.2004.05.188","article-title":"AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise","volume":"320","author":"M Kelly","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"E1242","DOI":"10.1152\/ajpendo.00382.2007","article-title":"Lack of AMPKalpha2 enhances pyruvate dehydrogenase activity during exercise","volume":"293","author":"DK Klein","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bbi.2012.10.011","article-title":"Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior","volume":"27","author":"A Quintana","year":"2013","journal-title":"Brain Behav Immun"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1002\/oby.21139","article-title":"Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training","volume":"23","author":"JG Knudsen","year":"2015","journal-title":"Obesity (Silver Spring)"},{"key":"ref36","article-title":"A flexible system of enzymatic analysis","author":"OH Lowry","year":"1972"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"8269","DOI":"10.1016\/S0021-9258(17)34391-0","article-title":"Enzyme patterns in single human muscle fibers","volume":"253","author":"CV Lowry","year":"1978","journal-title":"J Biol Chem"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"P Chomczynski","year":"1987","journal-title":"Anal Biochem"},{"key":"ref39","first-page":"148","article-title":"An improvement of the single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"8","author":"C Puissant","year":"1990","journal-title":"Biotechniques"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"E806","DOI":"10.1152\/ajpendo.2000.279.4.E806","article-title":"Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise","volume":"279","author":"H Pilegaard","year":"2000","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0003-2697(90)90292-H","article-title":"Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle","volume":"185","author":"G Cederblad","year":"1990","journal-title":"Anal Biochem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/0003-2697(91)90437-X","article-title":"A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue","volume":"198","author":"D Constantin-Teodosiu","year":"1991","journal-title":"Anal Biochem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"37223","DOI":"10.1074\/jbc.M103069200","article-title":"Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase","volume":"276","author":"LG Korotchkina","year":"2001","journal-title":"J Biol Chem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1113\/jphysiol.2004.081679","article-title":"AMP kinase activation with AICAR simultaneously increases fatty acid and glucose oxidation in resting rat soleus muscle","volume":"565","author":"AC Smith","year":"2005","journal-title":"J Physiol"},{"issue":"Pt 1","key":"ref45","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1469-7793.2000.t01-1-00221.x","article-title":"Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle","volume":"528","author":"JF Wojtaszewski","year":"2000","journal-title":"J Physiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1055\/s-2001-13818","article-title":"Tissue expression and plasma concentrations of TNFalpha, IL-1beta, and IL-6 following treadmill exercise in mice","volume":"22","author":"LH Colbert","year":"2001","journal-title":"Int J Sports Med"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1007\/s00125-010-1754-4","article-title":"IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise","volume":"53","author":"L Fritsche","year":"2010","journal-title":"Diabetologia"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1152\/japplphysiol.00551.2015","article-title":"Exercise-mediated IL-6 signaling occurs independent of inflammation and is amplified by training in mouse adipose tissue","volume":"119","author":"L Castellani","year":"2015","journal-title":"J Appl Physiol (1985)"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1748-1716.2011.02269.x","article-title":"Interleukin-6 modifies mRNA expression in mouse skeletal muscle","volume":"202","author":"H Adser","year":"2011","journal-title":"Acta Physiol (Oxf)"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.1038\/ncomms7047","article-title":"A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis","volume":"6","author":"SM Reilly","year":"2015","journal-title":"Nat Commun"},{"key":"ref51","first-page":"395","article-title":"STATs: An Old Story, Yet Mesmerizing","volume":"17","author":"S Abroun","year":"2015","journal-title":"Cell J"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2478\/v10039-011-0059-2","article-title":"Interleukin 6 is not necessary for STAT3 phosphorylation and myocardial hypertrophy following short term beta-adrenergic stimulation","volume":"57","author":"KA Kaminski","year":"2012","journal-title":"Adv Med Sci"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1210\/en.2003-1319","article-title":"Reduced exercise endurance in interleukin-6-deficient mice","volume":"145","author":"J Faldt","year":"2004","journal-title":"Endocrinology"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1113\/expphysiol.2012.065508","article-title":"Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice","volume":"97","author":"A Benrick","year":"2012","journal-title":"Exp Physiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0156460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T01:41:04Z","timestamp":1656726064000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0156460"}},"subtitle":[],"editor":[{"given":"Andrew","family":"Philp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,6,21]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0156460","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,21]]}}}