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The authors aimed to investigate whether the use of metformin, an AMPK activator, could reverse this metabolic remodeling in chronic AF and to explore the underlying mechanisms.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted chronic AF animal models with 18 beagle dogs and divided them into SR (pacemaker implanted without pacing), AF (pacemaker implanted with sustained pacing at a frequency of 400 beats\/min for 6\u2009weeks), and metformin+AF group (daily oral administration of metformin was initiated 1\u2009week before surgery and continued throughout the study period). After electrophysiological measurements, the left atrial appendage tissue samples were taken from the beating heart for further analysis. Protein expression, histological analysis, and biochemical measurements were conducted.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The AF groups showed decreased expression of FAT\/CD36, CPT-1, VLCAD, increased concentration of free fatty acid and triglyceride, and increased lipid deposition. The activation of AMPK\/PGC-1\u03b1\/PPAR\u03b1 pathway was decreased. The key factors of the Warburg effect, including HIF-1\u03b1, GLUT-1, PDK1, HK, and LDH, increased in AF group compared to SR group. The expression of PDH decreased significantly, accompanied by increased atrial lactate production. The extent of fibrosis increased significantly in the left atrial appendage of AF group. dERP, \u2211WOV, and AF inducibility increased while ERP decreased in AF group compared to SR group. The use of metformin attenuated all these changes effectively.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Metformin improves lipid metabolism and reverses the Warburg effect in chronic AF via AMPK activation. It attenuates atrial electrical and structural remodeling.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12872-020-01359-7","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T20:03:42Z","timestamp":1580760222000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation"],"prefix":"10.1186","volume":"20","author":[{"given":"Yaozhong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifan","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-2668","authenticated-orcid":false,"given":"Qiming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"issue":"1","key":"1359_CR1","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1152\/physrev.00031.2009","volume":"91","author":"U Schotten","year":"2011","unstructured":"Schotten U, Verheule S, Kirchhof P, Goette A. 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The research was carried out in accordance with the World Medical Association Declaration of Helsinki. The animal study was performed in strict accordance with the recommendations in Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee governing the Ethics of Animal Experiments of the Wuhan University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}