{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:31:14Z","timestamp":1789767074569,"version":"4.0.1"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Cinvestav","doi-asserted-by":"publisher","award":["A1-S-9082"],"award-info":[{"award-number":["A1-S-9082"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Cinvestav","doi-asserted-by":"publisher","award":["CF-2023-G-446"],"award-info":[{"award-number":["CF-2023-G-446"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Fondo Ciencia de Frontera 2023","doi-asserted-by":"publisher","award":["A1-S-9082"],"award-info":[{"award-number":["A1-S-9082"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Fondo Ciencia de Frontera 2023","doi-asserted-by":"publisher","award":["CF-2023-G-446"],"award-info":[{"award-number":["CF-2023-G-446"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic syndrome (MetS) is a worldwide problem affecting at least one-third of the population. MetS patients have increased cardiovascular risk associated with an abnormal \u03b2-adrenergic response; however, it is not clear how MetS affects the cardiac \u03b2-adrenergic system. We analyzed cardiac function and the \u03b2-adrenergic response in an experimental model of MetS in rats by recording pressure\u2013volume (PV) loops via an open-chest approach and performed a biochemical characterization of the cardiac \u03b2-adrenergic system through ELISA, radioligand binding assays, and Western blotting. Microscopy was employed to evaluate cardiac hypertrophy, fibrosis, and ultrastructure. MetS rats exhibited cardiac dysfunction, evidenced by a reduced cardiac output and ejection fraction, not explained by heart hypertrophy or fibrosis. MetS rats also had an elevated susceptibility to lethal arrhythmia following intra-cardiac administration of the non-selective \u03b2-adrenergic agonist isoproterenol, suggesting alterations in the \u03b2-adrenergic system. The total serum adrenaline and noradrenaline levels were higher in the MetS animals than those in the control group. The radioligand binding assays indicated no change in the \u03b2AR density; however, the Western blot analyses revealed decreased levels of G\u03b1s proteins and \u03b2-arrestin 1, but increased \u03b22AR and G\u03b1i protein levels. This study contributes to our understanding of how MetS can alter cardiac function, raising the risk of lethal arrhythmia induced by the \u03b2-adrenergic (fight or flight) response and underscores the relevance of therapeutically targeting MetS before its pathological progression toward cardiomyopathy.<\/jats:p>","DOI":"10.3390\/ijms26167989","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T11:41:41Z","timestamp":1755603701000},"page":"7989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered \u03b2-Adrenergic System, Cardiac Dysfunction, and Lethal Arrhythmia in a Rat Model of Metabolic Syndrome"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-4179","authenticated-orcid":false,"given":"Rommel","family":"S\u00e1nchez-Hern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies (Cinvestav) of the National Polytechnic Institute, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07300, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4484-5899","authenticated-orcid":false,"given":"Daphne E.","family":"Cruz-Villarreal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Research and Advanced Studies (Cinvestav) of the National Polytechnic Institute, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07300, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-7967","authenticated-orcid":false,"given":"Alejandro","family":"Silva-Palacios","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Ch\u00e1vez, Juan Badiano 1, Belisario Dom\u00ednguez Secc 16, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra-Mar\u00eda","family":"Z\u00fa\u00f1iga-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Ch\u00e1vez, Juan Badiano 1, Belisario Dom\u00ednguez Secc 16, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Soria-Castro","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Ch\u00e1vez, Juan Badiano 1, Belisario Dom\u00ednguez Secc 16, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0637-5239","authenticated-orcid":false,"given":"Carlos","family":"S\u00e1nchez-Garibay","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, National Institute of Neurology and Neurosurgery Manuel Velasco Su\u00e1rez, Insurgentes Sur 3877, La Fama, Tlalpan, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-316X","authenticated-orcid":false,"given":"Cecilia","family":"Zazueta","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Ch\u00e1vez, Juan Badiano 1, Belisario Dom\u00ednguez Secc 16, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-9274","authenticated-orcid":false,"given":"J. Alberto","family":"Olivares-Reyes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Research and Advanced Studies (Cinvestav) of the National Polytechnic Institute, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07300, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9-Antonio","family":"Arias-Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies (Cinvestav) of the National Polytechnic Institute, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07300, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-8494","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Rueda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Center for Research and Advanced Studies (Cinvestav) of the National Polytechnic Institute, Av. IPN 2508, San Pedro Zacatenco, Mexico City 07300, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"m2297","DOI":"10.1136\/bmj.m2297","article-title":"Association between Prediabetes and Risk of All Cause Mortality and Cardiovascular Disease: Updated Meta-Analysis","volume":"370","author":"Cai","year":"2020","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1007\/s00125-005-1798-z","article-title":"Neuroadrenergic and Reflex Abnormalities in Patients with Metabolic Syndrome","volume":"48","author":"Grassi","year":"2005","journal-title":"Diabetologia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1136\/heartjnl-2014-305685","article-title":"Metabolic Syndrome Is Associated with and Predicted by Resting Heart Rate: A Cross-Sectional and Longitudinal Study","volume":"101","author":"Jiang","year":"2015","journal-title":"Heart"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1053\/meta.2001.19502","article-title":"Urinary Epinephrine and Norepinephrine Interrelations with Obesity, Insulin, and the Metabolic Syndrome in Hong Kong Chinese","volume":"50","author":"Lee","year":"2001","journal-title":"Metabolism"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s00592-022-01945-5","article-title":"Heart Rate Thresholds for Cardiovascular Risk and Sympathetic Activation in the Metabolic Syndrome","volume":"59","author":"Seravalle","year":"2022","journal-title":"Acta Diabetol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S2213-8587(14)70033-6","article-title":"Metabolic Syndrome: A Sympathetic Disease?","volume":"3","author":"Schlaich","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_8","first-page":"S46","article-title":"The Concise Guide to Pharmacology 2019\/20: G Protein-coupled Receptors","volume":"176","author":"Alexander","year":"2019","journal-title":"Br. 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