{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:46:31Z","timestamp":1780429591904,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"am","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008902","name":"Los Alamos National Laboratory","doi-asserted-by":"publisher","award":["20230067DR"],"award-info":[{"award-number":["20230067DR"]}],"id":[{"id":"10.13039\/100008902","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Obesity continues to rise in the juveniles and obese children are more likely to develop metabolic syndrome (MetS) and related cardiovascular disease. Unfortunately, effective prevention and long\u2010term treatment options remain limited. We determined the juvenile cardiac response to MetS in a swine model. Juvenile male swine were fed either an obesogenic diet, to induce MetS, or a lean diet, as a control (LD). Myocardial ischemia was induced with surgically placed ameroid constrictor on the left circumflex artery. Physiological data were recorded and at 22\u2009weeks of age the animals underwent a terminal harvest procedure and myocardial tissue was extracted for total metabolic and proteomic LC\/MS\u2013MS, RNA\u2010seq analysis, and data underwent nonnegative matrix factorization for metabolic signatures. Significantly altered in MetS versus. LD were the glycolysis\u2010related metabolites and enzymes. In MetS compared with LD Glycogen synthase 1 (GYS1)\u2010glycogen phosphorylases (PYGM\/PYGL) expression disbalance resulted in a loss of myocardial glycogen. Our findings are consistent with the concept that transcriptionally driven myocardial changes in glycogen and glucose metabolism\u2010related enzymes lead to a deficiency of their metabolite products in MetS. This abnormal energy metabolism provides insight into the pathogenesis of the juvenile heart in MetS. This study reveals that MetS and ischemia diminishes ATP availability in the myocardium via altering the glucose\u2010G6P\u2010pyruvate axis at the level of metabolites and gene expression of related enzymes. The observed severe glycogen depletion in MetS coincides with disbalance in expression of GYS1 and both PYGM and PYGL. This altered energy substrate metabolism is a potential target of pharmacological agents for improving juvenile myocardial function in MetS and ischemia.<\/jats:p>","DOI":"10.14814\/phy2.15742","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T02:05:36Z","timestamp":1691114736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impaired cardiac glycolysis and glycogen depletion are linked to poor myocardial outcomes in juvenile male swine with metabolic syndrome and ischemia"],"prefix":"10.14814","volume":"11","author":[{"given":"Mark","family":"Broadwin","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight D.","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharif A.","family":"Sabe","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Sengun","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber J.","family":"Sylvestre","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boian S.","family":"Alexandrov","sequence":"additional","affiliation":[{"name":"Los Alamos National Laboratory  Los Alamos New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-801X","authenticated-orcid":false,"given":"Frank W.","family":"Sellke","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-2425","authenticated-orcid":false,"given":"Anny","family":"Usheva","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery Warren Alpert Medical School of Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.17.2239"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568008054064869"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00158.2021"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurpub\/ckv016"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2010.12.008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.5.1443"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.320334"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470747278"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2005.12.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.042"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13114176"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/b820820b"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.7.1654"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.07.027"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000014022.85836.96"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(98)06423\u2010x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201060387\u20107"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315180"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2002.2050"},{"issue":"4","key":"e_1_2_11_21_1","first-page":"300","article-title":"Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan swine","volume":"60","author":"Neeb Z. 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